Melatonin regulates the calcium-buffering proteins, parvalbumin and hippocalcin, in ischemic brain injury.
Melatonin has anti-oxidant activity and it exerts a neuroprotective effects during ischemic brain injury. Calcium-buffering proteins including parvalbumin and hippocalcin are involved in neuronal differentiation and maturation through calcium signaling. This study investigated whether melatonin moderates parvalbumin and hippocalcin expression in cerebral ischemia and glutamate toxicity-induced neuronal cell death. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were treated with vehicle or melatonin (5 mg/kg) prior to MCAO, and cerebral cortical tissues were collected 24 hr after MCAO. Parvalbumin and hippocalcin levels were decreased in vehicle-treated animal with MCAO, whereas melatonin prevented the ischemic injury-induced reduction in these proteins. In cultured hippocampal cells, glutamate toxicity decreased parvalbumin and hippocalcin levels, while melatonin treatment prevented the glutamate exposure-induced diminished in these proteins levels. Melatonin also attenuated the glutamate toxicity-induced increase in intracellular Ca(2+) levels. These results suggest that the maintenance of parvalbumin and hippocalcin levels by melatonin in ischemic injury contributes to the neuroprotective effect of melatonin against neuronal cell damage.
Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea. pokoh@gnu.ac.kr
Phil-Ok
PO
Koh
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000633:toxicity; D051597:Hippocalcin / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C496692:Hpca protein, mouse; C496693:Hpca protein, rat; D018696:Neuroprotective Agents; D010320:Parvalbumins; D051597:Hippocalcin; D018698:Glutamic Acid; D008550:Melatonin; D002118:Calcium