Neuroprotective effect of ginkgolide K on glutamate-induced cytotoxicity in PC 12 cells via inhibition of ROS generation and Ca(2+) influx.

Abstract

Glutamate is considered to be responsible for the pathogenesis of cerebral ischemia disease. [Ca(2+)](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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.

• Authors: Shuwei Ma, Hongxia Liu, Haoyan Jiao, Liyan Wang, Lvyi Chen, Jun Liang, Ming Zhao, Xiantao Zhang
• Journal: Neurotoxicology (Neurotoxicology) Vol. 33 Issue 1 Pg. 59-69 (Jan 2012) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 22120026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier B.V.

Chemical References

• Ginkgolides
• Lactones
• Neuroprotective Agents
• Neurotoxins
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• bcl-2-Associated X Protein
• ginkgolide K
• Glutamic Acid
• Malondialdehyde
• L-Lactate Dehydrogenase
• Glutathione Peroxidase
• Superoxide Dismutase
• Caspase 3
• Calcium

Topics

• Animals
• Apoptosis (drug effects)
• Calcium (metabolism)
• Caspase 3 (metabolism)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Drug Interactions
• Ginkgolides (chemistry, pharmacology)
• Glutamic Acid (toxicity)
• Glutathione Peroxidase (metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Lactones (chemistry, pharmacology)
• Malondialdehyde (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Neuroprotective Agents (pharmacology)
• Neurotoxins (toxicity)
• PC12 Cells (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)
• bcl-2-Associated X Protein (metabolism)