Carnosine protects against Abeta42-induced neurotoxicity in differentiated rat PC12 cells.
(1) The present study was designed to investigate whether histamine is involved in the protective effect of carnosine on Abeta42-induced impairment in differentiated PC12 cells. (2) PC12 cells were exposed to Abeta42 (5 muM) 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) Abeta42 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 Abeta42, 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 Abeta42-induced neurotoxicity is independent of the carnosine-histidine-histamine pathway, but may act through regulation of glutamate release and NMDA receptor trafficking.
Fu
Qiuli
Q
Department of Pharmacology, Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Dai
Haibin
H
Hu
Weiwei
W
Fan
Yanying
Y
Shen
Yao
Y
Zhang
Weiping
W
Chen
Zhong
Z
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology*; D002454:Cell Differentiation; D004155:Diphenhydramine / Q000494:pharmacology; D004347:Drug Interactions; D018698:Glutamic Acid / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D050198:Phenoxypropanolamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D009498:Neurotoxins; D010446:Peptide Fragments; D050198:Phenoxypropanolamines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D018698:Glutamic Acid; D004155:Diphenhydramine; D002336:Carnosine; D013890:Thiourea; C052075:thioperamide; C055302:zolantidine; C086108:clobenpropit