Acute exposure to ethanol potentiates human immunodeficiency virus type 1 Tat-induced Ca(2+) overload and neuronal death in cultured rat cortical neurons.
A significant number of human immunodeficiency virus type 1 (HIV-1)-infected patients are alcoholics. Either alcohol or HIV alone induces morphological and functional damage to the nervous system. HIV-1 Tat is a potent transcriptional activator of the viral promoter, with the ability to modulate a number of cellular regulatory circuits including apoptosis and to cause neuronal injury. To further evaluate the involvement of alcohol in neuronal injury, the authors examined the effect of ethanol on Tat-induced calcium responses in rat cerebral cortical neurons, using microfluorimetric calcium determination. HIV Tat protein (10 or 500 nM) elicited two types of calcium responses in cortical neurons: a fast-onset, short-lasting response and a slow-onset, sustained response. The responses were concentration-dependent and diminished in calcium-free saline. A short exposure to ethanol (50 mM) potentiated both types of calcium response, which was markedly decreased when the cells were pretreated with BAPTA-AM (20 microM). In addition, an increase in the neurotoxic effect of Tat, which was assessed by trypan blue exclusion assay, was observed. The result led the authors to conclude that alcohol exposure significantly potentiates Tat-induced calcium overload and neuronal death.
Brailoiu
Eugen
E
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. ebrailouy@temple.edu
Brailoiu
G Cristina
GC
Mameli
Giuseppe
G
Dolei
Antonina
A
Sawaya
Bassel E
BE
Dun
Nae J
NJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000821:virology; D000431:Ethanol / Q000494:pharmacology*; D015696:Gene Products, tat / Q000187:drug effects / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009474:Neurons / Q000166:cytology / Q000821:virology*; D051381:Rats; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D000431:Ethanol; D002118:Calcium