Source:http://linkedlifedata.com/resource/pubmed/id/11153078
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rdf:type | |
lifeskim:mentions |
umls-concept:C0017356,
umls-concept:C0019682,
umls-concept:C0019699,
umls-concept:C0027836,
umls-concept:C0033414,
umls-concept:C0086418,
umls-concept:C0162638,
umls-concept:C0332307,
umls-concept:C0441472,
umls-concept:C0596290,
umls-concept:C0752312,
umls-concept:C1150587,
umls-concept:C1367731,
umls-concept:C1370600,
umls-concept:C1456820,
umls-concept:C1705632
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pubmed:issue |
18
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pubmed:dateCreated |
2001-1-19
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pubmed:abstractText |
In neurodegenerative diseases associated with AIDS, reactive astrocytosis plays a central role in the neurotoxicity of the brain parenchyma. Whereas the HIV-1 nef gene is overexpressed during restricted HIV-1 infection of human astrocytes, our previous results have demonstrated that nef expressed in human U251MG glial cells activates the sphingomyelin pathway triggered by TNF-alpha, increasing ceramide production. Since ceramide is an important regulatory molecule of programmed cell death induced by TNF-alpha, we examined whether nef could alter TNF-alpha-induced apoptosis in the U251MG human astrocytoma cell line. Transfection studies indicated that nef could both prevent apoptosis and promote cell proliferation in response to TNF-alpha stimulation. MAPK and JNK activities were further analyzed in order to elucidate signaling cascades subsequent to the upregulation of ceramide production. After TNF-alpha treatment, both kinases were shown to be preferentially activated in the presence of nef. These experiments strongly suggest that the HIV-1 Nef protein might modulate the sensitivity of astrocytes to inflammatory molecules, thus contributing to the development of neurodegenerative diseases associated with AIDS.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, nef,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0889-2229
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1959-65
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11153078-Apoptosis,
pubmed-meshheading:11153078-Astrocytes,
pubmed-meshheading:11153078-Cell Division,
pubmed-meshheading:11153078-Enzyme Activation,
pubmed-meshheading:11153078-Gene Products, nef,
pubmed-meshheading:11153078-Genes, nef,
pubmed-meshheading:11153078-HIV-1,
pubmed-meshheading:11153078-Humans,
pubmed-meshheading:11153078-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:11153078-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11153078-Transfection,
pubmed-meshheading:11153078-Tumor Cells, Cultured,
pubmed-meshheading:11153078-Tumor Necrosis Factor-alpha,
pubmed-meshheading:11153078-nef Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2000
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pubmed:articleTitle |
HIV type 1 nef gene inhibits tumor necrosis factor alpha-induced apoptosis and promotes cell proliferation through the action of MAPK and JNK in human glial cells.
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pubmed:affiliation |
Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada G1V 4G2.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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