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result sql = The mitochondrial permeability transition, and oxidative and nitrosative stress in the mechanism of copper toxicity in cultured neurons and astrocytes.

The mitochondrial permeability transition, and oxidative and nitrosative stress in the mechanism of copper toxicity in cultured neurons and astrocytes.

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char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = y;code = 121
char = e;code = 101
char = ;code = 32
char = T;code = 84
char = M;code = 77
char = R;code = 82
char = E;code = 69
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 3;code = 51
char = 6;code = 54
char = %;code = 37
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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 = D;code = 68
char = e;code = 101
char = l;code = 108
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = P;code = 80
char = s;code = 115
char = i;code = 105
char = ;code = 32
char = m;code = 109
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 1;code = 49
char = 2;code = 50
char = ;code = 32
char = h;code = 104
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 = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 4;code = 52
char = 8;code = 56
char = %;code = 37
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = 7;code = 55
char = 2;code = 50
char = ;code = 32
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = b;code = 98
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = h;code = 104
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = P;code = 80
char = T;code = 84
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 4;code = 52
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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 = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
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 = l;code = 108
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = P;code = 80
char = T;code = 84
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 4;code = 52
char = 8;code = 56
char = -;code = 45
char = 7;code = 55
char = 5;code = 53
char = %;code = 37
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = );code = 41
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = r;code = 114
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = s;code = 115
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = l;code = 108
char = y;code = 121
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char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = C;code = 67
char = s;code = 115
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = a;code = 97
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char = h;code = 104
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = 2;code = 50
char = %;code = 37
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 4;code = 52
char = 8;code = 56
char = ;code = 32
char = h;code = 104
char = ,;code = 44
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char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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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 = b;code = 98
char = y;code = 121
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char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = i;code = 105
char = d;code = 100
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = 5;code = 53
char = -;code = 45
char = 6;code = 54
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char = %;code = 37
char = );code = 41
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = C;code = 67
char = s;code = 115
char = A;code = 65
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = 1;code = 49
char = %;code = 37
char = );code = 41
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 = 32
char = t;code = 116
char = o;code = 111
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char = a;code = 97
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = r;code = 114
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char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
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char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
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char = m;code = 109
char = P;code = 80
char = T;code = 84
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = a;code = 97
char = d;code = 100
char = ,;code = 44
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char = i;code = 105
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
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char = d;code = 100
char = ;code = 32
char = e;code = 101
char = a;code = 97
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char = l;code = 108
char = y;code = 121
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char = d;code = 100
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char = e;code = 101
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char = s;code = 115
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char = v;code = 118
char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = a;code = 97
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char = h;code = 104
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char = w;code = 119
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char = t;code = 116
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char = a;code = 97
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char = c;code = 99
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char = m;code = 109
char = i;code = 105
char = t;code = 116
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = (;code = 40
char = 6;code = 54
char = 3;code = 51
char = %;code = 37
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
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char = d;code = 100
char = e;code = 101
char = a;code = 97
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char = h;code = 104
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = a;code = 97
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char = x;code = 120
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char = d;code = 100
char = a;code = 97
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char = t;code = 116
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
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char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
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char = c;code = 99
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char = x;code = 120
char = i;code = 105
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char = s;code = 115
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char = a;code = 97
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char = e;code = 101
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
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char = s;code = 115
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char = b;code = 98
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char = t;code = 116
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = C;code = 67
char = s;code = 115
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = n;code = 110
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char = t;code = 116
char = y;code = 121
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char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = n;code = 110
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
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 = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = y;code = 121
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char = e;code = 101
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
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char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
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result sql = Copper is an essential element and an integral component of various enzymes. However, excess copper is neurotoxic and has been implicated in the pathogenesis of Wilson's disease, Alzheimer's disease, prion conditions, and other disorders. Although mechanisms of copper neurotoxicity are not fully understood, copper is known to cause oxidative stress and mitochondrial dysfunction. As oxidative stress is an important factor in the induction of the mitochondrial permeability transition (mPT), we determined whether mPT plays a role in copper-induced neural cell injury. Cultured astrocytes and neurons were treated with 20 microM copper and mPT was measured by changes in the cyclosporin A (CsA)-sensitive inner mitochondrial membrane potential (Delta Psi m), employing the potentiometric dye TMRE. In astrocytes, copper caused a 36% decrease in the Delta Psi m at 12 h, which decreased further to 48% by 24 h and remained at that level for at least 72 h. Cobalt quenching of calcein fluorescence as a measure of mPT similarly displayed a 45% decrease at 24 h. Pretreatment with antioxidants significantly blocked the copper-induced mPT by 48-75%. Copper (24 h) also caused a 30% reduction in ATP in astrocytes, which was completely blocked by CsA. Copper caused death (42%) in astrocytes by 48 h, which was reduced by antioxidants (35-60%) and CsA (41%). In contrast to astrocytes, copper did not induce mPT in neurons. Instead, it caused early and extensive death with a concomitant reduction (63%) in ATP by 14 h. Neuronal death was prevented by antioxidants and nitric oxide synthase inhibitors but not by CsA. Copper increased protein tyrosine nitration in both astrocytes and neurons. These studies indicate that mPT, and oxidative and nitrosative stress represent major factors in copper-induced toxicity in astrocytes, whereas oxidative and nitrosative stress appears to play a major role in neuronal injury.

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