|
|
char = N;code = 78
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char = P;code = 80
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char = x;code = 120
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result sql = NADPH oxidase drives cytokine and neurotoxin release from microglia and macrophages in response to HIV-Tat.
NADPH oxidase drives cytokine and neurotoxin release from microglia and macrophages in response to HIV-Tat.char = P;code = 80
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char = e;code = 101
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char = t;code = 116
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char = h;code = 104
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char = o;code = 111
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = i;code = 105
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char = (;code = 40
char = H;code = 72
char = I;code = 73
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char = );code = 41
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char = l;code = 108
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char = m;code = 109
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char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
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char = r;code = 114
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
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
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char = t;code = 116
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = t;code = 116
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char = a;code = 97
char = t;code = 116
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char = T;code = 84
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = m;code = 109
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char = o;code = 111
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char = o;code = 111
char = n;code = 110
char = s;code = 115
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char = o;code = 111
char = f;code = 102
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char = H;code = 72
char = I;code = 73
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char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
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char = T;code = 84
char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = r;code = 114
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char = n;code = 110
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char = l;code = 108
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char = m;code = 109
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char = e;code = 101
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char = i;code = 105
char = o;code = 111
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char = s;code = 115
char = h;code = 104
char = i;code = 105
char = p;code = 112
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char = b;code = 98
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char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = T;code = 84
char = a;code = 97
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char = i;code = 105
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char = e;code = 101
char = e;code = 101
char = ;code = 32
char = r;code = 114
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char = d;code = 100
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char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
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char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = l;code = 108
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char = s;code = 115
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char = j;code = 106
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char = t;code = 116
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char = s;code = 115
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char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = o;code = 111
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char = N;code = 78
char = A;code = 65
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char = f;code = 102
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char = N;code = 78
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result sql = Previous reports have shown that the human immunodeficiency virus (HIV) regulatory protein Tat has both pro-oxidant and pro-inflammatory properties, suggesting that Tat might contribute to the neurological complications of HIV. However, the intracellular mechanisms whereby Tat triggers free radical production and inflammation, and the relationship between Tat-induced free radicals and inflammatory reactions, are still subject to debate. The present study was undertaken to evaluate the specific effects of Tat on NADPH oxidase in microglia and macrophages, and to determine the specific role of NADPH oxidase in Tat-induced cytokine/chemokine release and neurotoxicity. Application of Tat to microglia or macrophages caused dose- and time-dependent increases in superoxide formation that were prevented by both pharmacologic NADPH oxidase inhibitors and by specific decoy peptides (gp91ds). Furthermore, inhibition of NADPH oxidase attenuated Tat-induced release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF), and monocyte chemoattractant protein 1 (MCP-1), and decreased microglial-mediated neurotoxicity. Finally, macrophages derived from NADPH oxidase-deficient mice displayed reduced superoxide production, released lower levels of cytokines/chemokines, and induced less neurotoxicity in response to Tat compared to wild-type macrophages. Together, these data describe a specific and biologically significant signaling component of the macrophage/microglial response to Tat, and suggest the neuropathology associated with HIV infection might originate in part with Tat-induced activation of NADPH oxidase.
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char = I;code = 73
char = V;code = 86
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char = T;code = 84
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char = .;code = 46
result sql = NADPH oxidase drives cytokine and neurotoxin release from microglia and macrophages in response to HIV-Tat.
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char = y;code = 121
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char = ;code = 32
char = (;code = 40
char = H;code = 72
char = I;code = 73
char = V;code = 86
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char = m;code = 109
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char = y;code = 121
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char = p;code = 112
char = r;code = 114
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char = ,;code = 44
char = ;code = 32
char = s;code = 115
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char = g;code = 103
char = e;code = 101
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char = i;code = 105
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = T;code = 84
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = m;code = 109
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char = t;code = 116
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char = e;code = 101
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char = e;code = 101
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char = l;code = 108
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = H;code = 72
char = I;code = 73
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char = .;code = 46
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char = H;code = 72
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char = e;code = 101
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char = e;code = 101
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char = T;code = 84
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char = ;code = 32
char = t;code = 116
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char = g;code = 103
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char = e;code = 101
char = e;code = 101
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char = r;code = 114
char = a;code = 97
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char = a;code = 97
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char = d;code = 100
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char = i;code = 105
char = n;code = 110
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char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
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char = i;code = 105
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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 = t;code = 116
char = h;code = 104
char = e;code = 101
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char = r;code = 114
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = i;code = 105
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char = b;code = 98
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char = ;code = 32
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char = a;code = 97
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char = e;code = 101
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char = r;code = 114
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char = i;code = 105
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char = l;code = 108
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char = m;code = 109
char = a;code = 97
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char = o;code = 111
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char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
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char = o;code = 111
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char = s;code = 115
char = ,;code = 44
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char = a;code = 97
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char = e;code = 101
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char = s;code = 115
char = t;code = 116
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char = l;code = 108
char = l;code = 108
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char = j;code = 106
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char = ;code = 32
char = t;code = 116
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char = d;code = 100
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char = b;code = 98
char = a;code = 97
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char = e;code = 101
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char = T;code = 84
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char = a;code = 97
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result sql = Previous reports have shown that the human immunodeficiency virus (HIV) regulatory protein Tat has both pro-oxidant and pro-inflammatory properties, suggesting that Tat might contribute to the neurological complications of HIV. However, the intracellular mechanisms whereby Tat triggers free radical production and inflammation, and the relationship between Tat-induced free radicals and inflammatory reactions, are still subject to debate. The present study was undertaken to evaluate the specific effects of Tat on NADPH oxidase in microglia and macrophages, and to determine the specific role of NADPH oxidase in Tat-induced cytokine/chemokine release and neurotoxicity. Application of Tat to microglia or macrophages caused dose- and time-dependent increases in superoxide formation that were prevented by both pharmacologic NADPH oxidase inhibitors and by specific decoy peptides (gp91ds). Furthermore, inhibition of NADPH oxidase attenuated Tat-induced release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF), and monocyte chemoattractant protein 1 (MCP-1), and decreased microglial-mediated neurotoxicity. Finally, macrophages derived from NADPH oxidase-deficient mice displayed reduced superoxide production, released lower levels of cytokines/chemokines, and induced less neurotoxicity in response to Tat compared to wild-type macrophages. Together, these data describe a specific and biologically significant signaling component of the macrophage/microglial response to Tat, and suggest the neuropathology associated with HIV infection might originate in part with Tat-induced activation of NADPH oxidase.
Publication: Antioxid. Redox Signal. 2009 Feb ;11(2)::193-204. :doi: 10.1089/ARS.2008.2097.
Publication Date: 2009 Feb
Study Author(s): Turchan-Cholewo, Jadwiga;Dimayuga, Vanessa M;Gupta, Sunita;Gorospe, R M Charlotte;Keller, Jeffrey N;Bruce-Keller, Annadora J;
Institution: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA.
Shortcut link to this study:
Publication Date: 2009 Feb
Study Author(s): Turchan-Cholewo, Jadwiga;Dimayuga, Vanessa M;Gupta, Sunita;Gorospe, R M Charlotte;Keller, Jeffrey N;Bruce-Keller, Annadora J;
Institution: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA.
Shortcut link to this study:
Previous reports have shown that the human immunodeficiency virus (HIV) regulatory protein Tat has both pro-oxidant and pro-inflammatory properties, suggesting that Tat might contribute to the neurological complications of HIV. However, the intracellular mechanisms whereby Tat triggers free radical production and inflammation, and the relationship between Tat-induced free radicals and inflammatory reactions, are still subject to debate. The present study was undertaken to evaluate the specific effects of Tat on NADPH oxidase in microglia and macrophages, and to determine the specific role of NADPH oxidase in Tat-induced cytokine/chemokine release and neurotoxicity. Application of Tat to microglia or macrophages caused dose- and time-dependent increases in superoxide formation that were prevented by both pharmacologic NADPH oxidase inhibitors and by specific decoy peptides (gp91ds). Furthermore, inhibition of NADPH oxidase attenuated Tat-induced release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF), and monocyte chemoattractant protein 1 (MCP-1), and decreased microglial-mediated neurotoxicity. Finally, macrophages derived from NADPH oxidase-deficient mice displayed reduced superoxide production, released lower levels of cytokines/chemokines, and induced less neurotoxicity in response to Tat compared to wild-type macrophages. Together, these data describe a specific and biologically significant signaling component of the macrophage/microglial response to Tat, and suggest the neuropathology associated with HIV infection might originate in part with Tat-induced activation of NADPH oxidase.
PMID: 18715150
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