char = R;code = 82
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = l;code = 108
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 = c;code = 99
char = o;code = 111
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
result sql = Reversibility of covalent electrophile-protein adducts and chemical toxicity.
Reversibility of covalent electrophile-protein adducts and chemical toxicity.
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = 1;code = 49
char = -;code = 45
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = -;code = 45
char = 4;code = 52
char = -;code = 45
char = (;code = 40
char = 4;code = 52
char = ';code = 39
char = -;code = 45
char = [;code = 91
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = h;code = 104
char = e;code = 101
char = x;code = 120
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ];code = 93
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
char = x;code = 120
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = );code = 41
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = B;code = 66
char = M;code = 77
char = C;code = 67
char = C;code = 67
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = o;code = 111
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = -;code = 45
char = N;code = 78
char = -;code = 45
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = h;code = 104
char = e;code = 101
char = x;code = 120
char = y;code = 121
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = A;code = 65
char = B;code = 66
char = );code = 41
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
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 = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = I;code = 73
char = A;code = 65
char = B;code = 66
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = E;code = 69
char = K;code = 75
char = 2;code = 50
char = 9;code = 57
char = 3;code = 51
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = M;code = 77
char = C;code = 67
char = C;code = 67
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = M;code = 77
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = B;code = 66
char = M;code = 77
char = C;code = 67
char = C;code = 67
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = u;code = 117
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = B;code = 66
char = M;code = 77
char = C;code = 67
char = C;code = 67
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = D;code = 68
char = H;code = 72
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = D;code = 68
char = P;code = 80
char = H;code = 72
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = I;code = 73
char = A;code = 65
char = B;code = 66
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = u;code = 117
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
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
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = B;code = 66
char = M;code = 77
char = C;code = 67
char = C;code = 67
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = C;code = 67
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
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result sql = The biotin-tagged electrophiles 1-biotinamido-4-(4'-[maleimidoethylcyclohexane]-carboxamido)butane (BMCC) and N-iodoacetyl-N-biotinylhexylenediamine (IAB) have been used as model electrophile probes in complex proteomes to identify protein targets associated with chemical toxicity. Whereas IAB activates stress signaling and apoptosis in HEK293 cells, BMCC does not. Cysteine Michael adducts formed from BMCC and nonbiotinylated analogues rapidly disappeared in the intact cells, whereas the adducts were stable in BMCC-treated subcellular fractions, even in the presence of the cellular reductants reduced glutathione, NADH, and NADPH. In contrast, cysteine thioether adducts formed from IAB and its nonbiotinylated analogues were stable in intact cells. Loss of the BMCC adduct in cells was reduced at 4 degrees C, which suggests the involvement of a metabolic process in adduct removal. Model studies with a glutathione-BMCC conjugate indicated rapid hydrolysis of the adducted imide ring, but neither the conjugate nor its hydrolysis product dissociated to release the electrophile in neutral aqueous buffer at significant rates. The results suggest that low BMCC toxicity reflects facile repair that results in transient adduction, which fails to trigger damage-signaling pathways.

Publication: Chem. Res. Toxicol. 2008 Dec ;21(12)::2361-9.
Publication Date: 2008 Dec
Study Author(s): Lin, De;Saleh, Samir;Liebler, Daniel C;
Institution: Department of Biochemistry, Vanderbilt Institute for Chemical Biology, Vanderbilt University School of Medicine, U1213C Medical Research Building III, 465 21st Avenue South, Nashville, Tennessee 37232, USA.
Shortcut link to this study:
The biotin-tagged electrophiles 1-biotinamido-4-(4'-[maleimidoethylcyclohexane]-carboxamido)butane (BMCC) and N-iodoacetyl-N-biotinylhexylenediamine (IAB) have been used as model electrophile probes in complex proteomes to identify protein targets associated with chemical toxicity. Whereas IAB activates stress signaling and apoptosis in HEK293 cells, BMCC does not. Cysteine Michael adducts formed from BMCC and nonbiotinylated analogues rapidly disappeared in the intact cells, whereas the adducts were stable in BMCC-treated subcellular fractions, even in the presence of the cellular reductants reduced glutathione, NADH, and NADPH. In contrast, cysteine thioether adducts formed from IAB and its nonbiotinylated analogues were stable in intact cells. Loss of the BMCC adduct in cells was reduced at 4 degrees C, which suggests the involvement of a metabolic process in adduct removal. Model studies with a glutathione-BMCC conjugate indicated rapid hydrolysis of the adducted imide ring, but neither the conjugate nor its hydrolysis product dissociated to release the electrophile in neutral aqueous buffer at significant rates. The results suggest that low BMCC toxicity reflects facile repair that results in transient adduction, which fails to trigger damage-signaling pathways.
PMID: 19548357

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