Neuroprotective effect of ginkgolide K on glutamate-induced cytotoxicity in PC 12 cells via inhibition of ROS generation and Ca(2+) influx |
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Authors: | Ma Shuwei Liu Hongxia Jiao Haoyan Wang Liyan Chen Lvyi Liang Jun Zhao Ming Zhang Xiantao |
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Affiliation: | a Pharmaceutical Engineering, Institute of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006, PR China b Guangdong Research Institute of Traditional Chinese Medicine, No. 321 Longdong Northern Road, Guangzhou 510009, PR China c School of Pharmacy, South-Central University for Nationalities, Wuhan 430074, PR China |
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Abstract: | Glutamate is considered to be responsible for the pathogenesis of cerebral ischemia disease. [Ca2+]i influx and reactive oxygen species (ROS) production are considered to be involved in glutamate-induced apoptosis process. In this study, we investigated the neuroprotective effects of ginkgolide K in the glutamate-induced rat's adrenal pheochromocytoma cell line (PC 12 cells) and the possible mechanism. Glutamate cytotoxicity in PC 12 cells was accompanied by an increment of malondialdehyde (MDA) content and lactate dehydrogenase (LDH) release, as well as Ca2+ influx, bax/bcl-2 ratio, cytochrome c release, caspase-3 protein and ROS generation, and reduction of cell viability and mitochondrial membrane potential (MMP). Moreover, treatment with glutamate alone resulted in decrease activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity. However, pretreatment with ginkgolide K significantly reduced MDA content, LDH release, as well as Ca2+ influx, cytochrome c release, bax/bcl-2 ratio, caspase-3 protein and ROS production, and attenuated the decrease of cells viability and MMP. In addition, ginkgolide K remarkedly up-regulated SOD and GSH-PX activities. All these findings indicated that ginkgolide K protected PC12 cells against glutamate-induced apoptosis by inhibiting Ca2+ influx and ROS production. Therefore, the present study supports the notion that ginkgolide K may be a promising neuroprotective agent for the treatment of cerebral ischemia disease. |
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Keywords: | Ginkgolide K PC 12 cells Ca2+ ROS Bax protein Bcl-2 protein Caspase-3 protein |
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