HIV-1 COAT PROTEIN NEUROTOXICITY PREVENTED BY CALCIUM-CHANNEL ANTAGONISTS

被引：573

作者：

DREYER, EB

KAISER, PK

OFFERMANN, JT

LIPTON, SA

机构：

[1] HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115

[2] HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02215

[3] HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115

[4] HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115

[5] HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02115

来源：

SCIENCE | 1990年 / 248卷 / 4953期

关键词：

D O I：

10.1126/science.2326646

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Coat protein gp120 from the human immunodeficiency virus type-1 (HIV-1) increased intracellular free calcium and injured rodent retinal ganglion cells and hippocampal neurons in culture. Highly purified recombinant gp120 envelope protein produced these effects in a dose-dependent fashion at picomolar concentrations. Immunoprecipitation with antibody to gp120, but not with control immunoglobulin-containing serum, depleted solutions of the viral envelope protein and also prevented both the rise in intracellular calcium and neuronal toxicity. The gp120-induced increase in intracellular calcium was abrogated by transiently lowering extracellular calcium or by adding the dihydropyridine calcium channel antagonist nimodipine (100 nM). Calcium channel antagonists also prevented gp120-induced neuronal injury. In addition, intracellular stores appeared to contribute substantially to the increase in calcium elicited by gp120. Since increases in intracellular calcium have been associated with neurotoxicity, it is possible that an injurious effect of gp120 on neurons might be related to this mechanism and that treatment with calcium channel antagonists may prove useful in mitigating HIV-1-related neuronal injury.

引用

页码：364 / 367

页数：4

共 39 条

[1] NITRENDIPINE BLOCK OF CARDIAC CALCIUM CHANNELS - HIGH-AFFINITY BINDING TO THE INACTIVATED STATE [J].