Abstract:
:Infection by the human immunodeficiency virus type 1 (HIV-1) often results in neurological dysfunction including HIV dementia (HIVD). Alterations in cytokine and redox balance are thought to play important roles in the pathogenesis of HIVD, but the specific mechanisms underlying neuronal dysfunction and death are unknown. Activation of cytokine receptors and oxidative stress can induce the production of ceramide from membrane sphingomyelin, and recent findings suggest that ceramide is an important mediator of a form of programmed cell death called apoptosis. We now report that levels of ceramide, sphingomyelin, and hydroxynonenal (HNE) are significantly increased in brain tissues and cerebrospinal fluid of HIVD patients. Exposure of cultured neurons to the neurotoxic HIV proteins gp120 and Tat resulted in increased cellular levels of sphingomyelin, ceramide, and HNE. The ceramide precursor palmitoyl-CoA sensitized neurons to Tat and gp120 toxicity, whereas an inhibitor of ceramide production reduced Tat and gp120-induced increases of ceramide and HNE and protected the neurons from Tat and gp120-induced death. These results suggest that HIV-1 infection may promote a lipid imbalance in neural cells, resulting in an overproduction of ceramide and consequent cellular dysfunction and death.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Haughey NJ,Cutler RG,Tamara A,McArthur JC,Vargas DL,Pardo CA,Turchan J,Nath A,Mattson MPdoi
10.1002/ana.10828keywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
257-67issue
2eissn
0364-5134issn
1531-8249journal_volume
55pub_type
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journal_title:Annals of neurology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title:Annals of neurology
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410060612
更新日期:1979-12-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1002/ana.25641
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pub_type: 杂志文章
doi:10.1002/ana.410060308
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pub_type: 杂志文章
doi:10.1002/1531-8249(199901)45:1<75::aid-art13>3.0.co
更新日期:1999-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/ana.410070304
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journal_title:Annals of neurology
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更新日期:1987-07-01 00:00:00
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更新日期:2016-12-01 00:00:00
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更新日期:2006-08-01 00:00:00
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journal_title:Annals of neurology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1997-06-01 00:00:00
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journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
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更新日期:1997-03-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2012-01-01 00:00:00