char = M;code = 77
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = C;code = 67
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = t;code = 116
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 = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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 = 46
result sql = Membrane cholesterol content modulates ClC-2 gating and sensitivity to oxidative stress.
Membrane cholesterol content modulates ClC-2 gating and sensitivity to oxidative stress.
char = C;code = 67
char = l;code = 108
char = C;code = 67
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = a;code = 97
char = d;code = 100
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = h;code = 104
char = e;code = 101
char = ;code = 32
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = -;code = 45
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = C;code = 67
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
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char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = 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 = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = C;code = 67
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = C;code = 67
char = -;code = 45
char = 2;code = 50
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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 = i;code = 105
char = b;code = 98
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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 = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
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char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = e;code = 101
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char = e;code = 101
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
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char = e;code = 101
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = -;code = 45
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = D;code = 68
char = S;code = 83
char = M;code = 77
char = );code = 41
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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 = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = d;code = 100
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 = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = u;code = 117
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = O;code = 79
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = P;code = 80
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = n;code = 110
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char = .;code = 46
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = C;code = 67
char = -;code = 45
char = 2;code = 50
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = o;code = 111
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char = d;code = 100
char = ;code = 32
char = c;code = 99
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char = c;code = 99
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char = d;code = 100
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char = i;code = 105
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char = ;code = 32
char = d;code = 100
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char = e;code = 101
char = r;code = 114
char = g;code = 103
char = e;code = 101
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char = -;code = 45
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char = b;code = 98
char = l;code = 108
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char = m;code = 109
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char = b;code = 98
char = a;code = 97
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = n;code = 110
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
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char = l;code = 108
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = D;code = 68
char = S;code = 83
char = M;code = 77
char = ;code = 32
char = u;code = 117
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char = o;code = 111
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char = ;code = 32
char = c;code = 99
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char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = c;code = 99
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char = t;code = 116
char = r;code = 114
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char = n;code = 110
char = .;code = 46
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char = A;code = 65
char = s;code = 115
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char = a;code = 97
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char = s;code = 115
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char = s;code = 115
char = s;code = 115
char = e;code = 101
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char = b;code = 98
char = y;code = 121
char = ;code = 32
char = p;code = 112
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char = ;code = 32
char = c;code = 99
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char = c;code = 99
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char = h;code = 104
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char = l;code = 108
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = s;code = 115
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char = i;code = 105
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char = d;code = 100
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result sql = ClC-2 is a broadly expressed member of the voltage-gated ClC chloride channel family. In this study, we aimed to evaluate the role of the membrane lipid environment in ClC-2 function, and in particular the effect of cholesterol and ClC-2 distribution in membrane microdomains. Detergent-resistant and detergent-soluble microdomains (DSM) were isolated from stably transfected HEK293 cells by a discontinuous OptiPrep gradient. ClC-2 was found concentrated in detergent-insoluble membranes in basal conditions and relocalized to DSM upon cholesterol depletion by methyl-beta-cyclodextrin. As assessed by patch clamp recordings, relocalization was accompanied by acceleration of the activation kinetics of the channel. A similar distribution and activation pattern were obtained when cells were treated with the oxidant tert-butyl hydroperoxide and after ATP depletion. In both cases activation was prevented by cholesterol enrichment of cells. We conclude that the cholesterol environment regulates ClC-2 activity, and we provide evidence that the increase in ClC-2 activity in response to acute oxidative or metabolic stress involves relocalization of this channel to DSM.

Publication: J. Biol. Chem. 2007 Jan 26 ;282(4)::2423-32.
Publication Date: 2007 Jan 26
Study Author(s): Hinzpeter, Alexandre;Fritsch, Janine;Borot, Florence;Trudel, Stéphanie;Vieu, Diane-Lore;Brouillard, Franck;Baudouin-Legros, Maryvonne;Clain, Jérôme;Edelman, Aleksander;Ollero, Mario;
Institution: INSERM, U806, Université Paris-Descartes, Faculté de Médecine René Descartes, F-75015 Paris, France.
Shortcut link to this study:
ClC-2 is a broadly expressed member of the voltage-gated ClC chloride channel family. In this study, we aimed to evaluate the role of the membrane lipid environment in ClC-2 function, and in particular the effect of cholesterol and ClC-2 distribution in membrane microdomains. Detergent-resistant and detergent-soluble microdomains (DSM) were isolated from stably transfected HEK293 cells by a discontinuous OptiPrep gradient. ClC-2 was found concentrated in detergent-insoluble membranes in basal conditions and relocalized to DSM upon cholesterol depletion by methyl-beta-cyclodextrin. As assessed by patch clamp recordings, relocalization was accompanied by acceleration of the activation kinetics of the channel. A similar distribution and activation pattern were obtained when cells were treated with the oxidant tert-butyl hydroperoxide and after ATP depletion. In both cases activation was prevented by cholesterol enrichment of cells. We conclude that the cholesterol environment regulates ClC-2 activity, and we provide evidence that the increase in ClC-2 activity in response to acute oxidative or metabolic stress involves relocalization of this channel to DSM.
PMID: 17110372

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