Neuroprotective effect of carnosine on necrotic cell death in PC12 cells.
The nervous tissue of many vertebrates, including humans, can synthesize beta-alanyl-L-histidine (carnosine). The biological functions of carnosine are still open to question, although several theories supported by strong experimental data have been proposed. The objective of this study was to examine the effects of carnosine on neurotoxicity in differentiated rat pheochromocytoma (PC12) cells. Neurotoxicity was induced by N-methyl-D-aspartate (NMDA), which caused time- and concentration-dependent cell death as measured by MTT and LDH assays. Pretreatment with carnosine significantly prevented the neurotoxicity in a concentration-dependent manner. The protective effect of carnosine was antagonized by the H1 receptor antagonist pyrilamine, but not by the H2 receptor antagonist cimetidine. In addition, alpha-fluoromethylhistidine, a histidine decarboxylase inhibitor, slightly reversed the protective action of carnosine. These results indicate that carnosine can effectively protect against NMDA-induced necrosis in PC12 cells, and its protection may in part be due to the activation of the postsynaptic histamine H1 receptor. The study suggests that carnosine may be an endogenous protective factor and calls for its further study as a new anti-excitotoxic agent.
Shen
Yao
Y
Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, and Department of Pharmacy, Second Affiliated Hospital, Hangzhou 310058, China.
Fan
Yanying
Y
Dai
Haibin
H
Fu
Qiuli
Q
Hu
Weiwei
W
Chen
Zhong
Z
D000818:Animals; D002336:Carnosine / Q000378:metabolism / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008762:Methylhistidines / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D009336:Necrosis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D016716:PC12 Cells; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D006634:Histamine H1 Antagonists; D008762:Methylhistidines; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011969:Receptors, Histamine H1; D016202:N-Methylaspartate; C028309:alpha-fluoromethylhistidine; D002336:Carnosine; D011738:Pyrilamine