title: Estradiol alleviates the ischemic brain injury-induced decrease of neuronal calcium sensor protein hippocalcin.
abstract: Estradiol has protective and reparative effects in neurodegenerative diseases. Hippocalcin is a neuronal calcium-sensor protein that acts as a calcium buffer to regulate the intracellular concentration of Ca(2+). This study was investigated to elucidate whether estradiol regulates hippocalcin expression in a focal cerebral ischemia model and glutamate-treated neuronal cells. An ovariectomy was performed in adult female rats, and vehicle or estradiol was administered before middle cerebral artery occlusion (MCAO). Cerebral cortex tissues were collected at 24h after MCAO. A proteomic approach revealed that hippocalcin expression decreased in vehicle-treated animals with combined MCAO, while estradiol treatment attenuated this decrease. Reverse transcription-PCR and Western blot analyses also showed that estradiol administration prevented the MCAO injury-induced decrease in hippocalcin expression. In cultured hippocampal cells, glutamate exposure increased the intracellular Ca(2+) concentration, which was rescued by the presence of estradiol. Moreover, glutamate toxicity decreased hippocalcin expression, whereas estradiol attenuated this decrease. Together, these findings suggest that estradiol has a neuroprotective function by regulating hippocalcin expression and intracellular Ca(2+) levels in ischemic brain injury.
authors.affiliation: Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, 501 Jinjudaero, Jinju 660-701, Gyeongnam, South Korea. Electronic address: pokoh@gnu.ac.kr.
authors.forename: Phil-Ok
authors.initials: PO
authors.lastname: Koh
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D051597:Hippocalcin / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D051379:Mice; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D020543:Proteome; D051597:Hippocalcin; D018698:Glutamic Acid; D004958:Estradiol; D002118:Calcium
keywords: Estradiol; Hippocalcin; Neuroprotection