The Metabotropic Glutamate Receptor System Protects Against Ischemic Free Radical Programed Cell Death in Rat Brain Endothelial Cells

来自 EBSCO

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摘要：

As one of the key determinants of ischemic injury, cerebrovascular endothelial (EC) degeneration may be dependent upon the generation of the free radical nitric (NO) and the subsequent (). Although the mechanisms that can prevent EC injury are most likely multifactorial in origin, the () system may represent a novel therapeutic approach for ECs given the ability of the system to reverse neuronal injury. This study examined the modulation of individual subtypes of during and NO toxicity in primary cerebrovascular ECs. injury was determined through dye exclusion, dehydrogenase release, DNA fragmentation, (PS) exposure, and . , through the generation of NO, and exposure to exogenous NO were directly toxic to ECs. Exposure to NO rapidly decreased EC viability from 98% +/- 2% to 40% +/- 9%, increased DNA fragmentation from 2% +/- 2% to 61% +/- 9%, and increased PS exposure from 3% +/- 3% to 66% +/- 6% over a 24-hour period. Activation of the system significantly increased EC survival through the prevention of NO-induced DNA fragmentation and PS residue exposure. In contrast, antagonism of the system failed to prevent . Cytoprotection by the system was dependent, at least in part, upon the direct inhibition of NO-generated - and -like activities. Further investigation into the ability of the system to prevent in ECs may open new therapeutic avenues for the treatment of cerebrovascular injury.

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关键词：

Apoptosis Cysteine proteases DNA fragmentation Endothelial cells Metabotropic glutamate receptors Phosphatidylserine

DOI：

10.1097/00004647-200103000-00010

被引量：

219

年份：

2001