|
|
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char = c;code = 99
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char = l;code = 108
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char = o;code = 111
char = n;code = 110
char = .;code = 46
result sql = Aplidin induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation.
Aplidin induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation.char = A;code = 65
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char = ;code = 32
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char = R;code = 82
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char = l;code = 108
char = e;code = 101
char = x;code = 120
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = c;code = 99
char = 1;code = 49
char = ;code = 32
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 = o;code = 111
char = r;code = 114
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
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char = A;code = 65
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
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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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
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 = 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
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
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
char = t;code = 116
char = ;code = 32
char = A;code = 65
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
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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
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char = y;code = 121
char = ;code = 32
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 = 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 = G;code = 71
char = S;code = 83
char = S;code = 83
char = G;code = 71
char = /;code = 47
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
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char = t;code = 116
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char = o;code = 111
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char = ;code = 32
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char = ;code = 32
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char = c;code = 99
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char = s;code = 115
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char = ;code = 32
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = p;code = 112
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
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char = u;code = 117
char = s;code = 115
char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
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 = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = c;code = 99
char = 1;code = 49
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = K;code = 75
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
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 = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Aplidin is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulation of Rac1 by transfection of small interfering RNA (siRNA) duplexes or the use of a specific Rac1 inhibitor decreased Aplidin-induced JNK activation and cytotoxicity. Our results show that Aplidin induces apoptosis by increasing the GSSG/GSH ratio, a necessary step for induction of oxidative stress and sustained JNK activation through Rac1 activation and MKP-1 downregulation.
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
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
char = s;code = 115
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
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 = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
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char = a;code = 97
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = t;code = 116
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char = t;code = 116
char = h;code = 104
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char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = h;code = 104
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 = R;code = 82
char = a;code = 97
char = c;code = 99
char = 1;code = 49
char = ;code = 32
char = G;code = 71
char = T;code = 84
char = P;code = 80
char = a;code = 97
char = s;code = 115
char = e;code = 101
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 = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = K;code = 75
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = d;code = 100
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char = w;code = 119
char = n;code = 110
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char = e;code = 101
char = g;code = 103
char = u;code = 117
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
result sql = Aplidin induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation.
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result sql = Aplidin is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulation of Rac1 by transfection of small interfering RNA (siRNA) duplexes or the use of a specific Rac1 inhibitor decreased Aplidin-induced JNK activation and cytotoxicity. Our results show that Aplidin induces apoptosis by increasing the GSSG/GSH ratio, a necessary step for induction of oxidative stress and sustained JNK activation through Rac1 activation and MKP-1 downregulation.
Publication: Cell Death Differ. 2006 Nov ;13(11)::1968-81.
Publication Date: 2006 Nov
Study Author(s): González-Santiago, L;Suárez, Y;Zarich, N;Muñoz-Alonso, M J;Cuadrado, A;Martínez, T;Goya, L;Iradi, A;Sáez-Tormo, G;Maier, J V;Moorthy, A;Cato, A C B;Rojas, J M;Muñoz, A;
Institution: Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Arturo Duperier, 4, Madrid E-28029, Spain.
Shortcut link to this study:
Publication Date: 2006 Nov
Study Author(s): González-Santiago, L;Suárez, Y;Zarich, N;Muñoz-Alonso, M J;Cuadrado, A;Martínez, T;Goya, L;Iradi, A;Sáez-Tormo, G;Maier, J V;Moorthy, A;Cato, A C B;Rojas, J M;Muñoz, A;
Institution: Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Arturo Duperier, 4, Madrid E-28029, Spain.
Shortcut link to this study:
Aplidin is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulation of Rac1 by transfection of small interfering RNA (siRNA) duplexes or the use of a specific Rac1 inhibitor decreased Aplidin-induced JNK activation and cytotoxicity. Our results show that Aplidin induces apoptosis by increasing the GSSG/GSH ratio, a necessary step for induction of oxidative stress and sustained JNK activation through Rac1 activation and MKP-1 downregulation.
PMID: 16543941
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