Carnosine Protects Against A Beta 42-Induced Neurotoxicity In Differentiated Rat Pc12 Cells
Cellular and molecular neurobiology(2008)
摘要
(1) The present study was designed to investigate whether histamine is involved in the protective effect of carnosine on A beta 42-induced impairment in differentiated PC12 cells. (2) PC12 cells were exposed to A beta 42 (5 mu M) for 24 h after carnosine (5 mM) applied for 18 h. Histamine receptor antagonists (diphenhydramine, zolantidine, thioperamide, clobenpropit) or histidine decarboxylase inhibitor (alpha-fluoromethylhistidine) were added 15 min before carnosine. Cell viability, glutamate release or cell surface expression of NMDA receptor was examined. (3) A beta 42 caused a concentration-dependent reduction of viability in PC12 cells and pretreatment with carnosine ameliorated this impairment. This amelioration was reversed by the H-3 receptor antagonists thioperamide and clobenpropit, but not by either the H-1 receptor antagonist diphenhydramine or the H-2 receptor antagonist zolantidine. Further, alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, also had no effect. In the presence of A beta 42, carnosine significantly decreased glutamate release and carnosine increased the surface expression of NMDA receptor. (4) These results indicate that the mechanism by which carnosine attenuates A beta 42-induced neurotoxicity is independent of the carnosine-histidine-histamine pathway, but may act through regulation of glutamate release and NMDA receptor trafficking.
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关键词
carnosine,Alzheimer's disease,histamine,A beta 42,NMDA receptor,trafficking,neurotoxicity
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