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result sql = The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease.
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result sql = Tetrahydroisoquinoline (TIQ) derivatives are putative neurotoxins that may contribute to the degeneration of dopaminergic neurons in Parkinson's disease. One TIQ, norsalsolinol (NorSAL), is present in dopamine-rich areas of human brain, including the substantia nigra. Here, we demonstrate that NorSAL reduces cell viability and induces apoptosis via cytochrome c release and caspase 3 activation in SH-SY5Y human neuroblastoma cells. Cytochrome c release, caspase 3 activation, and apoptosis induction were all inhibited by the antioxidant N-acetylcysteine. Thus, reactive oxygen species (ROS) contribute to apoptosis induced by NorSAL. Treatment with NorSAL also increased levels of oxidative damage to DNA, a stimulus for apoptosis, in SH-SY5Y. To clarify the mechanism of intracellular DNA damage, we examined the DNA damage caused by NorSAL using (32)P-5'-end-labeled isolated DNA fragments. NorSAL induced DNA damage in the presence of Cu(II). Catalase and bathocuproine, a Cu(I) chelator, inhibited this DNA damage, suggesting that ROS such as the Cu(I)-hydroperoxo complex derived from the reaction of H(2)O(2) with Cu(I), promote DNA damage by NorSAL. In summary, NorSAL-generated ROS induced oxidative DNA damage, which led to caspase-dependent apoptosis in neuronal cells.
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result sql = The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease.
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char = s;code = 115
char = e;code = 101
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char = i;code = 105
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char = c;code = 99
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char = a;code = 97
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char = e;code = 101
char = a;code = 97
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = u;code = 117
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char = a;code = 97
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
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char = i;code = 105
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char = e;code = 101
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char = s;code = 115
char = u;code = 117
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char = s;code = 115
char = t;code = 116
char = a;code = 97
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char = a;code = 97
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char = i;code = 105
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char = r;code = 114
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
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char = d;code = 100
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = r;code = 114
char = S;code = 83
char = A;code = 65
char = L;code = 76
char = ;code = 32
char = r;code = 114
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char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = s;code = 115
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char = c;code = 99
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char = l;code = 108
char = l;code = 108
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char = v;code = 118
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char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
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char = ;code = 32
char = i;code = 105
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char = u;code = 117
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char = s;code = 115
char = ;code = 32
char = a;code = 97
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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 = v;code = 118
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = y;code = 121
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char = o;code = 111
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = e;code = 101
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char = c;code = 99
char = ;code = 32
char = r;code = 114
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char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = a;code = 97
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char = c;code = 99
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = 3;code = 51
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 = 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 = S;code = 83
char = H;code = 72
char = -;code = 45
char = S;code = 83
char = Y;code = 89
char = 5;code = 53
char = Y;code = 89
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
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 = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = a;code = 97
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 = C;code = 67
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = c;code = 99
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char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = a;code = 97
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char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = ,;code = 44
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = a;code = 97
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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
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
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char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
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char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
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char = b;code = 98
char = y;code = 121
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
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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 = ;code = 32
char = N;code = 78
char = -;code = 45
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 = 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 = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = u;code = 117
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = r;code = 114
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char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = o;code = 111
char = x;code = 120
char = y;code = 121
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char = e;code = 101
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char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = R;code = 82
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char = S;code = 83
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char = ;code = 32
char = c;code = 99
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char = ;code = 32
char = a;code = 97
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char = o;code = 111
char = p;code = 112
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char = o;code = 111
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char = s;code = 115
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char = e;code = 101
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char = b;code = 98
char = y;code = 121
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char = N;code = 78
char = o;code = 111
char = r;code = 114
char = S;code = 83
char = A;code = 65
char = L;code = 76
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = r;code = 114
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char = a;code = 97
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char = m;code = 109
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char = t;code = 116
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = r;code = 114
char = S;code = 83
char = A;code = 65
char = L;code = 76
char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = o;code = 111
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
char = l;code = 108
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char = f;code = 102
char = ;code = 32
char = o;code = 111
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char = d;code = 100
char = a;code = 97
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char = i;code = 105
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char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = u;code = 117
char = s;code = 115
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char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = a;code = 97
char = p;code = 112
char = o;code = 111
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char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = S;code = 83
char = H;code = 72
char = -;code = 45
char = S;code = 83
char = Y;code = 89
char = 5;code = 53
char = Y;code = 89
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = f;code = 102
char = y;code = 121
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
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char = a;code = 97
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char = i;code = 105
char = s;code = 115
char = m;code = 109
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = D;code = 68
char = N;code = 78
char = A;code = 65
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char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
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char = e;code = 101
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char = ;code = 32
char = w;code = 119
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char = e;code = 101
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = D;code = 68
char = N;code = 78
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char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
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char = e;code = 101
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char = a;code = 97
char = u;code = 117
char = s;code = 115
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char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = N;code = 78
char = o;code = 111
char = r;code = 114
char = S;code = 83
char = A;code = 65
char = L;code = 76
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
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char = (;code = 40
char = 3;code = 51
char = 2;code = 50
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char = P;code = 80
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char = ';code = 39
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char = e;code = 101
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char = t;code = 116
char = s;code = 115
char = .;code = 46
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char = N;code = 78
char = o;code = 111
char = r;code = 114
char = S;code = 83
char = A;code = 65
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char = o;code = 111
char = f;code = 102
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char = C;code = 67
char = u;code = 117
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char = I;code = 73
char = I;code = 73
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char = .;code = 46
char = ;code = 32
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char = a;code = 97
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char = a;code = 97
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char = C;code = 67
char = u;code = 117
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char = c;code = 99
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char = e;code = 101
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char = a;code = 97
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char = t;code = 116
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char = s;code = 115
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char = D;code = 68
char = N;code = 78
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char = d;code = 100
char = a;code = 97
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char = a;code = 97
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char = h;code = 104
char = a;code = 97
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char = R;code = 82
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = C;code = 67
char = u;code = 117
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char = I;code = 73
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char = -;code = 45
char = h;code = 104
char = y;code = 121
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char = x;code = 120
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char = m;code = 109
char = p;code = 112
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char = v;code = 118
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char = f;code = 102
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char = o;code = 111
char = m;code = 109
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char = h;code = 104
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char = r;code = 114
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = H;code = 72
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result sql = Tetrahydroisoquinoline (TIQ) derivatives are putative neurotoxins that may contribute to the degeneration of dopaminergic neurons in Parkinson's disease. One TIQ, norsalsolinol (NorSAL), is present in dopamine-rich areas of human brain, including the substantia nigra. Here, we demonstrate that NorSAL reduces cell viability and induces apoptosis via cytochrome c release and caspase 3 activation in SH-SY5Y human neuroblastoma cells. Cytochrome c release, caspase 3 activation, and apoptosis induction were all inhibited by the antioxidant N-acetylcysteine. Thus, reactive oxygen species (ROS) contribute to apoptosis induced by NorSAL. Treatment with NorSAL also increased levels of oxidative damage to DNA, a stimulus for apoptosis, in SH-SY5Y. To clarify the mechanism of intracellular DNA damage, we examined the DNA damage caused by NorSAL using (32)P-5'-end-labeled isolated DNA fragments. NorSAL induced DNA damage in the presence of Cu(II). Catalase and bathocuproine, a Cu(I) chelator, inhibited this DNA damage, suggesting that ROS such as the Cu(I)-hydroperoxo complex derived from the reaction of H(2)O(2) with Cu(I), promote DNA damage by NorSAL. In summary, NorSAL-generated ROS induced oxidative DNA damage, which led to caspase-dependent apoptosis in neuronal cells.
Publication: J. Neurochem. 2009 Jan ;108(2)::397-407. :doi: 10.1111/j.1471-4159.2008.05774.x.
Publication Date: 2009 Jan
Study Author(s): Kobayashi, Hatasu;Fukuhara, Kiyoshi;Tada-Oikawa, Saeko;Yada, Yuki;Hiraku, Yusuke;Murata, Mariko;Oikawa, Shinji;
Institution: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan.
Shortcut link to this study:
Publication Date: 2009 Jan
Study Author(s): Kobayashi, Hatasu;Fukuhara, Kiyoshi;Tada-Oikawa, Saeko;Yada, Yuki;Hiraku, Yusuke;Murata, Mariko;Oikawa, Shinji;
Institution: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan.
Shortcut link to this study:
Tetrahydroisoquinoline (TIQ) derivatives are putative neurotoxins that may contribute to the degeneration of dopaminergic neurons in Parkinson's disease. One TIQ, norsalsolinol (NorSAL), is present in dopamine-rich areas of human brain, including the substantia nigra. Here, we demonstrate that NorSAL reduces cell viability and induces apoptosis via cytochrome c release and caspase 3 activation in SH-SY5Y human neuroblastoma cells. Cytochrome c release, caspase 3 activation, and apoptosis induction were all inhibited by the antioxidant N-acetylcysteine. Thus, reactive oxygen species (ROS) contribute to apoptosis induced by NorSAL. Treatment with NorSAL also increased levels of oxidative damage to DNA, a stimulus for apoptosis, in SH-SY5Y. To clarify the mechanism of intracellular DNA damage, we examined the DNA damage caused by NorSAL using (32)P-5'-end-labeled isolated DNA fragments. NorSAL induced DNA damage in the presence of Cu(II). Catalase and bathocuproine, a Cu(I) chelator, inhibited this DNA damage, suggesting that ROS such as the Cu(I)-hydroperoxo complex derived from the reaction of H(2)O(2) with Cu(I), promote DNA damage by NorSAL. In summary, NorSAL-generated ROS induced oxidative DNA damage, which led to caspase-dependent apoptosis in neuronal cells.
PMID: 19012744
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