Calcium acts as a second messenger that mediates physiologic functions, such as metabolism, cell proliferation, and apoptosis. Hippocalcin is a neuronal calcium sensor protein that regulates intracellular calcium concentration. Moreover, it prevents neuronal cell death from oxidative stress. Quercetin has excellent antioxidant properties and preventative effects. We studied modulation of hippocalcin expression by quercetin treatment in cerebral ischemic injury and glutamate-induced neuronal cell damage. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats were injected with vehicle or quercetin (10 mg/kg) 1 h prior to pMCAO, and cerebral cortical tissues were isolated 24 h after pMCAO. Quercetin improved pMCAO-induced neuronal movement deficit and infarction. pMCAO induced a decrease in hippocalcin expression in the cerebral cortex. However, quercetin treatment attenuated this pMCAO-induced decrease. In cultured hippocampal cells, glutamate excitotoxicity dramatically increased the intracellular calcium concentration, whereas quercetin alleviated intracellular calcium overload. Moreover, Western blot and immunocytochemical studies showed reduction of hippocalcin expression in glutamate-exposed cells. Quercetin prevented this glutamate-induced decrease. Furthermore, caspase-3 expression in hippocalcin siRNA transfection conditions is higher than caspase-3 expression in un-transfection conditions. Quercetin treatment attenuated the increase of caspase-3. Taken together, these results suggest that quercetin exerts a preventative effect through attenuation of intracellular calcium overload and restoration of down-regulated hippocalcin expression during ischemic injury.

中文翻译：

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槲皮素通过防止缺血引起的神经元钙传感器蛋白Hippocalcin减少而减少缺血性脑损伤。

钙作为第二信使，介导生理功能，例如新陈代谢，细胞增殖和凋亡。河马钙素是调节细胞内钙浓度的神经元钙传感器蛋白。此外，它可以防止神经细胞因氧化应激而死亡。槲皮素具有出色的抗氧化性能和预防作用。我们研究了槲皮素治疗脑缺血性损伤和谷氨酸诱导的神经元细胞损伤中河马降钙素表达的调节。局灶性脑缺血是由永久性大脑中动脉闭塞（pMCAO）引起的。在雄性Sprague-Dawley大鼠中，在pMCAO前1小时注射媒介物或槲皮素（10 mg / kg），并在pMCAO后24小时分离大脑皮层组织。槲皮素改善了pMCAO引起的神经元运动缺陷和梗塞。pMCAO诱导大脑皮层中河马钙蛋白表达降低。然而，槲皮素治疗减弱了该pMCAO诱导的下降。在培养的海马细胞中，谷氨酸兴奋性毒性极大地增加了细胞内钙的浓度，而槲皮素减轻了细胞内钙的超负荷。此外，蛋白质印迹和免疫细胞化学研究表明，谷氨酸暴露的细胞中河马钙蛋白表达降低。槲皮素阻止了谷氨酸引起的减少。此外，在河马钙素siRNA转染条件下，caspase-3表达高于未转染条件下的caspase-3表达。槲皮素处理减弱了caspase-3的增加。在一起