gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine.

Abstract:

:After incubation of rat cortical cell cultures with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 12 h, cells showed fragmentation of DNA at internucleosomal linkers, the characteristic feature of apoptosis. In a quantitative approach, it was determined that the percentage of DNA fragmentation increased from 7%, in the absence of gp120, to 62% following incubation with 24 ng/ml of gp120. Simultaneously, the percentage of viable cells decreased from 94% to 33%. Memantine (1-amino-3,5-dimethyladamantane), a drug currently used in the therapy of spasticity and Parkinson's disease as well as the NMDA antagonist MK-801 both prevented the effects of gp120 at micromolar concentrations. In human cultured astrocytes, gp120 was ineffective with respect to DNA fragmentation and cell toxicity. From these data, we conclude that the gp120-induced apoptosis may contribute to the neurological complications frequently associated with the immunodeficiency syndrome. The cytoprotective effect of memantine in cortical cell cultures may qualify the drug for the treatment of AIDS-related dementia.

journal_name

Eur J Pharmacol

authors

Müller WE,Schröder HC,Ushijima H,Dapper J,Bormann J

doi

10.1016/0922-4106(92)90063-2

keywords:

subject

Has Abstract

pub_date

1992-07-01 00:00:00

pages

209-14

issue

3

eissn

0014-2999

issn

1879-0712

journal_volume

226

pub_type

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