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char = b;code = 98
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char = .;code = 46
result sql = Differential cardiotoxic/cardioprotective effects of beta-adrenergic receptor subtypes in myocytes and fibroblasts in doxorubicin cardiomyopathy.
Differential cardiotoxic/cardioprotective effects of beta-adrenergic receptor subtypes in myocytes and fibroblasts in doxorubicin cardiomyopathy.
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char = s;code = 115
char = s;code = 115
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 = 44
char = ;code = 32
char = P;code = 80
char = <;code = 60
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 5;code = 53
char = );code = 41
char = ;;code = 59
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = /;code = 47
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = m;code = 109
char = y;code = 121
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 = 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 = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = 1;code = 49
char = 1;code = 49
char = %;code = 37
char = ;;code = 59
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = /;code = 47
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = 1;code = 49
char = 8;code = 56
char = %;code = 37
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = W;code = 87
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = P;code = 80
char = <;code = 60
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 5;code = 53
char = );code = 41
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = T;code = 84
char = U;code = 85
char = N;code = 78
char = E;code = 69
char = L;code = 76
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = s;code = 115
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 = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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 = ;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 = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = s;code = 115
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
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 = (;code = 40
char = W;code = 87
char = T;code = 84
char = ;code = 32
char = 2;code = 50
char = 6;code = 54
char = %;code = 37
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 = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = i;code = 105
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = 4;code = 52
char = 5;code = 53
char = .;code = 46
char = 9;code = 57
char = %;code = 37
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = /;code = 47
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = 1;code = 49
char = 6;code = 54
char = .;code = 46
char = 8;code = 56
char = %;code = 37
char = ,;code = 44
char = ;code = 32
char = P;code = 80
char = <;code = 60
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 5;code = 53
char = );code = 41
char = .;code = 46
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = F;code = 70
char = i;code = 105
char = b;code = 98
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 = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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 = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
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 = P;code = 80
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = u;code = 117
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = W;code = 87
char = T;code = 84
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 = 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 = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
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 = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ,;code = 44
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 = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = G;code = 71
char = i;code = 105
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 = 46
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = t;code = 116
char = i;code = 105
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 = 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 = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = m;code = 109
char = y;code = 121
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 = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
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 = 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 = i;code = 105
char = o;code = 111
char = n;code = 110
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
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 = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = /;code = 47
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
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 = ;code = 32
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 = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = ;code = 32
char = v;code = 118
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = A;code = 65
char = R;code = 82
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = l;code = 108
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 = ;code = 32
char = m;code = 109
char = y;code = 121
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 = i;code = 105
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = t;code = 116
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 2;code = 50
char = -;code = 45
char = A;code = 65
char = R;code = 82
char = s;code = 115
char = ;code = 32
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 = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
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 = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = -;code = 45
char = A;code = 65
char = R;code = 82
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
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 = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = beta-Adrenoceptor (beta-AR) subtypes act through different signaling pathways to regulate cardiac function and remodeling. Previous in vivo data show a markedly enhanced cardiotoxic response to doxorubicin in beta2-/- mice, which is rescued by the additional deletion of the beta1-AR. We determined whether this differential response was myocyte specific by examining the effects of doxorubicin in myocytes and fibroblasts from WT and beta1, beta2 and beta1/beta2-/- mice. Cells were exposed to doxorubicin at 1-50 microM and viability and apoptosis assessed at 6, 24 and 48 h. WT myocytes showed a time and dose-dependent decrease in viability (42% decrease at 1 microM after 24 h). beta2-/- Myocytes showed a greater decrease in viability vs. WT (20.8% less at 6 h; 14% less at 24 h, P<0.05); beta1-/- and beta1/beta2-/- myocytes showed enhanced survival (beta1-/- 11%; beta1/beta2-/- 18% greater than WT, P<0.05) TUNEL : staining demonstrated a similar differential susceptibility (WT 26% apoptotic nuclei, beta2-/- 45.9%, beta1/beta2-/- 16.8%, P<0.05). beta2-/- Fibroblasts also showed enhanced toxicity. Pertussis toxin pretreatment of WT cells decreased survival similar to the beta2-/-, suggesting a role for Gi signaling. JNK was differentially activated in beta2-/- myocytes after doxorubicin and its inhibition increased cardiotoxicity. In conclusion, the differential cardioprotective/cardiotoxic effects mediated by beta1 vs. beta2-AR subtypes in knockout mice are recapitulated in myocytes isolated from these mice. beta2-ARs appear to play a cardioprotective role, whereas beta1-ARs a cardiotoxic role.

Publication: J. Mol. Cell. Cardiol. 2006 Mar ;40(3)::375-83.
Publication Date: 2006 Mar
Study Author(s): Fajardo, Giovanni;Zhao, Mingming;Powers, Jennifer;Bernstein, Daniel;
Institution: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Shortcut link to this study:
beta-Adrenoceptor (beta-AR) subtypes act through different signaling pathways to regulate cardiac function and remodeling. Previous in vivo data show a markedly enhanced cardiotoxic response to doxorubicin in beta2-/- mice, which is rescued by the additional deletion of the beta1-AR. We determined whether this differential response was myocyte specific by examining the effects of doxorubicin in myocytes and fibroblasts from WT and beta1, beta2 and beta1/beta2-/- mice. Cells were exposed to doxorubicin at 1-50 microM and viability and apoptosis assessed at 6, 24 and 48 h. WT myocytes showed a time and dose-dependent decrease in viability (42% decrease at 1 microM after 24 h). beta2-/- Myocytes showed a greater decrease in viability vs. WT (20.8% less at 6 h; 14% less at 24 h, P<0.05); beta1-/- and beta1/beta2-/- myocytes showed enhanced survival (beta1-/- 11%; beta1/beta2-/- 18% greater than WT, P<0.05) TUNEL : staining demonstrated a similar differential susceptibility (WT 26% apoptotic nuclei, beta2-/- 45.9%, beta1/beta2-/- 16.8%, P<0.05). beta2-/- Fibroblasts also showed enhanced toxicity. Pertussis toxin pretreatment of WT cells decreased survival similar to the beta2-/-, suggesting a role for Gi signaling. JNK was differentially activated in beta2-/- myocytes after doxorubicin and its inhibition increased cardiotoxicity. In conclusion, the differential cardioprotective/cardiotoxic effects mediated by beta1 vs. beta2-AR subtypes in knockout mice are recapitulated in myocytes isolated from these mice. beta2-ARs appear to play a cardioprotective role, whereas beta1-ARs a cardiotoxic role.
PMID: 16458323

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