Mitochondria influence Fas expression in gp120-induced apoptosis of neuronal cells.
The human immunodeficiency virus-1 (HIV-1) destroys the immune system and also induces neurological disease culminating into dementia (HIV-associated dementia). Though the HIV viral protein gp120 induces apoptosis in neuronal cells, the mechanism of action is still poorly defined. Recent studies show that cells die during apoptosis by Fas aggregation aided by the mitochondrial proapoptotic proteins. Our studies show an increase in expression of Fas and its associated downstream proteins after treatment of the neuroblastoma cells, SH-SY5Y, with gp120. Fas and its associated death proteins, FADD and caspase-8 (DISC), are downregulated when treated with the caspase inhibitors. The results indicate that mitochondrial-death proteins like caspases may influence the upregulation of the death receptor Fas, and the inhibition of caspases prevents gp120-induced apoptosis.
Thomas
Sunil
S
Immunobiology Center, Mount Sinai School of Medicine, New York, NY, USA. sunthoma@utmb.edu
Mayer
Lloyd
L
Sperber
Kirk
K
D015526:AIDS Dementia Complex / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D015699:HIV Envelope Protein gp120; D019014:fas Receptor; C514793:gp120 protein, Human immunodeficiency virus 1; D053181:Caspase 8