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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = t;code = 116
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char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = H;code = 72
char = U;code = 85
char = V;code = 86
char = E;code = 69
char = C;code = 67
char = );code = 41
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = -;code = 45
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
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char = p;code = 112
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char = p;code = 112
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = s;code = 115
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = n;code = 110
char = a;code = 97
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = h;code = 104
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
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char = e;code = 101
char = i;code = 105
char = t;code = 116
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char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = n;code = 110
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = i;code = 105
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char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = a;code = 97
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char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = a;code = 97
char = l;code = 108
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char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
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char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = h;code = 104
char = e;code = 101
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = d;code = 100
char = i;code = 105
char = s;code = 115
char = u;code = 117
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char = p;code = 112
char = h;code = 104
char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = b;code = 98
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = e;code = 101
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char = o;code = 111
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char = e;code = 101
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char = i;code = 105
char = a;code = 97
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char = l;code = 108
char = l;code = 108
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char = u;code = 117
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char = e;code = 101
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char = r;code = 114
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char = i;code = 105
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char = o;code = 111
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char = h;code = 104
char = y;code = 121
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char = i;code = 105
char = o;code = 111
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char = r;code = 114
char = a;code = 97
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char = i;code = 105
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
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char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = a;code = 97
char = s;code = 115
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char = e;code = 101
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char = z;code = 122
char = y;code = 121
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = a;code = 97
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char = e;code = 101
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char = i;code = 105
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char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = -;code = 45
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
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char = h;code = 104
char = a;code = 97
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = O;code = 79
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
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char = t;code = 116
char = s;code = 115
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char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = t;code = 116
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char = e;code = 101
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = -;code = 45
char = a;code = 97
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char = g;code = 103
char = i;code = 105
char = o;code = 111
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char = e;code = 101
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char = c;code = 99
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = ;code = 32
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result sql = BACKGROUND : The prostate produces high levels of prostate-specific antigen (PSA), which has been shown to exert anti-angiogenic properties and thus might slow down prostate tumor growth. It has been suggested that the protease activity of PSA is not needed for its anti-angiogenic function. We have previously shown that seminal fluid contains both active and inactive, internally cleaved forms of PSA. The precise structural differences between these isoforms and their function are not known.
METHODS : To elucidate the structures, we purified PSA from seminal fluid and separated it by anion-exchange chromatography into six different isoforms, which were characterized by mass spectrometry. The anti-angiogenic activity of these PSA-isoforms was analyzed by human umbilical vein endothelial cell (HUVEC) tube formation assay.
RESULTS : The enzymatically active PSA-isoforms had an intact peptide moiety but could be separated into three isoforms based on differences in glycosylation. The major isoform contained PSA with a biantennary carbohydrate with terminal sialic acids on both antennae. The other active isoforms showed significant carbohydrate heterogeneity, containing one or no sialic acid. The inactive isoforms were internally cleaved at several different positions, but the fragments were held together by disulphide bonds. The enzymatic activity of PSA correlated with its inhibitory effect on the endothelial cell tube formation and the inhibition was dose-dependent at physiological concentrations, whereas enzymatically inactive internally cleaved PSA-isoforms had no effect.
CONCLUSIONS : Our results show that the anti-angiogenic effect of PSA is based on its proteolytic activity.
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char = .;code = 46
result sql = Structural characterization and anti-angiogenic properties of prostate-specific antigen isoforms in seminal fluid.
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char = i;code = 105
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char = v;code = 118
char = i;code = 105
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = h;code = 104
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char = s;code = 115
char = e;code = 101
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char = P;code = 80
char = S;code = 83
char = A;code = 65
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char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
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char = m;code = 109
char = s;code = 115
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = a;code = 97
char = l;code = 108
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char = z;code = 122
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char = b;code = 98
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char = h;code = 104
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char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = m;code = 109
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char = i;code = 105
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
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char = e;code = 101
char = i;code = 105
char = n;code = 110
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char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
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char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = H;code = 72
char = U;code = 85
char = V;code = 86
char = E;code = 69
char = C;code = 67
char = );code = 41
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = b;code = 98
char = e;code = 101
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char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = P;code = 80
char = S;code = 83
char = A;code = 65
char = -;code = 45
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = n;code = 110
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char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = a;code = 97
char = n;code = 110
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char = e;code = 101
char = n;code = 110
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
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char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
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char = y;code = 121
char = d;code = 100
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
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char = n;code = 110
char = a;code = 97
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char = ;code = 32
char = s;code = 115
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char = a;code = 97
char = l;code = 108
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
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char = d;code = 100
char = s;code = 115
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char = o;code = 111
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char = b;code = 98
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char = a;code = 97
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char = t;code = 116
char = e;code = 101
char = n;code = 110
char = n;code = 110
char = a;code = 97
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char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = t;code = 116
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char = e;code = 101
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char = a;code = 97
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char = f;code = 102
char = o;code = 111
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char = m;code = 109
char = s;code = 115
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char = s;code = 115
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char = o;code = 111
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char = e;code = 101
char = d;code = 100
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char = s;code = 115
char = i;code = 105
char = g;code = 103
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char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = t;code = 116
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char = c;code = 99
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char = b;code = 98
char = o;code = 111
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char = y;code = 121
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char = a;code = 97
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char = h;code = 104
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char = e;code = 101
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char = o;code = 111
char = g;code = 103
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char = a;code = 97
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char = n;code = 110
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char = e;code = 101
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char = o;code = 111
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char = s;code = 115
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char = a;code = 97
char = l;code = 108
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
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char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = a;code = 97
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char = v;code = 118
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char = f;code = 102
char = o;code = 111
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char = m;code = 109
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char = e;code = 101
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char = e;code = 101
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char = a;code = 97
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char = l;code = 108
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char = e;code = 101
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char = e;code = 101
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char = e;code = 101
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char = a;code = 97
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char = f;code = 102
char = f;code = 102
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char = p;code = 112
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char = s;code = 115
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char = i;code = 105
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char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = f;code = 102
char = r;code = 114
char = a;code = 97
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char = m;code = 109
char = e;code = 101
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char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
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char = e;code = 101
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char = h;code = 104
char = e;code = 101
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char = o;code = 111
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char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = s;code = 115
char = u;code = 117
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char = p;code = 112
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char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = b;code = 98
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
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char = c;code = 99
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = f;code = 102
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char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = z;code = 122
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char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = l;code = 108
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char = a;code = 97
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char = v;code = 118
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char = e;code = 101
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char = n;code = 110
char = a;code = 97
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char = y;code = 121
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char = e;code = 101
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = A;code = 65
char = -;code = 45
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = o;code = 111
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char = ;code = 32
char = h;code = 104
char = a;code = 97
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
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char = h;code = 104
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char = o;code = 111
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char = ;code = 32
char = a;code = 97
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result sql = BACKGROUND : The prostate produces high levels of prostate-specific antigen (PSA), which has been shown to exert anti-angiogenic properties and thus might slow down prostate tumor growth. It has been suggested that the protease activity of PSA is not needed for its anti-angiogenic function. We have previously shown that seminal fluid contains both active and inactive, internally cleaved forms of PSA. The precise structural differences between these isoforms and their function are not known.
METHODS : To elucidate the structures, we purified PSA from seminal fluid and separated it by anion-exchange chromatography into six different isoforms, which were characterized by mass spectrometry. The anti-angiogenic activity of these PSA-isoforms was analyzed by human umbilical vein endothelial cell (HUVEC) tube formation assay.
RESULTS : The enzymatically active PSA-isoforms had an intact peptide moiety but could be separated into three isoforms based on differences in glycosylation. The major isoform contained PSA with a biantennary carbohydrate with terminal sialic acids on both antennae. The other active isoforms showed significant carbohydrate heterogeneity, containing one or no sialic acid. The inactive isoforms were internally cleaved at several different positions, but the fragments were held together by disulphide bonds. The enzymatic activity of PSA correlated with its inhibitory effect on the endothelial cell tube formation and the inhibition was dose-dependent at physiological concentrations, whereas enzymatically inactive internally cleaved PSA-isoforms had no effect.
CONCLUSIONS : Our results show that the anti-angiogenic effect of PSA is based on its proteolytic activity.
Publication: Prostate 2008 Jun 15 ;68(9)::945-54. :doi: 10.1002/pros.20751.
Publication Date: 2008 Jun 15
Study Author(s): Mattsson, Johanna M;Valmu, Leena;Laakkonen, Pirjo;Stenman, Ulf-Håkan;Koistinen, Hannu;
Institution: Department of Clinical Chemistry, Biomedicum Helsinki, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Shortcut link to this study:
Publication Date: 2008 Jun 15
Study Author(s): Mattsson, Johanna M;Valmu, Leena;Laakkonen, Pirjo;Stenman, Ulf-Håkan;Koistinen, Hannu;
Institution: Department of Clinical Chemistry, Biomedicum Helsinki, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Shortcut link to this study:
BACKGROUND : The prostate produces high levels of prostate-specific antigen (PSA), which has been shown to exert anti-angiogenic properties and thus might slow down prostate tumor growth. It has been suggested that the protease activity of PSA is not needed for its anti-angiogenic function. We have previously shown that seminal fluid contains both active and inactive, internally cleaved forms of PSA. The precise structural differences between these isoforms and their function are not known.
METHODS : To elucidate the structures, we purified PSA from seminal fluid and separated it by anion-exchange chromatography into six different isoforms, which were characterized by mass spectrometry. The anti-angiogenic activity of these PSA-isoforms was analyzed by human umbilical vein endothelial cell (HUVEC) tube formation assay.
RESULTS : The enzymatically active PSA-isoforms had an intact peptide moiety but could be separated into three isoforms based on differences in glycosylation. The major isoform contained PSA with a biantennary carbohydrate with terminal sialic acids on both antennae. The other active isoforms showed significant carbohydrate heterogeneity, containing one or no sialic acid. The inactive isoforms were internally cleaved at several different positions, but the fragments were held together by disulphide bonds. The enzymatic activity of PSA correlated with its inhibitory effect on the endothelial cell tube formation and the inhibition was dose-dependent at physiological concentrations, whereas enzymatically inactive internally cleaved PSA-isoforms had no effect.
CONCLUSIONS : Our results show that the anti-angiogenic effect of PSA is based on its proteolytic activity.
METHODS : To elucidate the structures, we purified PSA from seminal fluid and separated it by anion-exchange chromatography into six different isoforms, which were characterized by mass spectrometry. The anti-angiogenic activity of these PSA-isoforms was analyzed by human umbilical vein endothelial cell (HUVEC) tube formation assay.
RESULTS : The enzymatically active PSA-isoforms had an intact peptide moiety but could be separated into three isoforms based on differences in glycosylation. The major isoform contained PSA with a biantennary carbohydrate with terminal sialic acids on both antennae. The other active isoforms showed significant carbohydrate heterogeneity, containing one or no sialic acid. The inactive isoforms were internally cleaved at several different positions, but the fragments were held together by disulphide bonds. The enzymatic activity of PSA correlated with its inhibitory effect on the endothelial cell tube formation and the inhibition was dose-dependent at physiological concentrations, whereas enzymatically inactive internally cleaved PSA-isoforms had no effect.
CONCLUSIONS : Our results show that the anti-angiogenic effect of PSA is based on its proteolytic activity.
PMID: 18386289
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