title: Neuroprotective effect of muscone on glutamate-induced apoptosis in PC12 cells via antioxidant and Ca(2+) antagonism.
abstract: In the pathogenesis of cerebral ischemia, glutamate excitotoxicity activates N-methyl-d-aspartate (NMDA) receptors which induce calcium influx and oxidative stress. Muscone exerts potent neuroprotective activities on cerebral ischemia. However, its underlying mechanism is yet to be elucidated. In this study, we demonstrated that pretreatment with muscone in PC12 cells markedly ameliorated the loss of cell viability, mitochondrial membrane potential (MMP) collapse, the release of lactate dehydrogenase (LDH), Ca(2+) overload, reactive oxygen species (ROS) generation, and cell apoptosis induced by glutamate. Furthermore, muscone also decreased NR1 (NMDA receptor subunit 1) protein expression, the ratio of Bax/Bcl-2 protein expression and prevented activitation of Ca(2+)/calmodulin-dependent protein kinase type II (CaMKII) and ASK1/JNK/p38 signaling pathways elicited by glutamate in PC12 cells. In conclusion, our results provided novel evidence that muscone protected PC12 cells against glutamate-induced apoptosis by attenuating ROS generation and Ca(2+) influx, via NR1 and CaMKII-depended ASK-1/JNK/p38 signaling pathways.
authors.affiliation: College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230031, PR China; Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei 230031, PR China; Anhui Key Laboratory of Modernized Chinese Material, Anhui University of Chinese Medicine, Hefei 230031, PR China.
authors.forename: Linchen
authors.initials: L
authors.lastname: Yu
authors.affiliation: College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230031, PR China; Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei 230031, PR China; Anhui Key Laboratory of Modernized Chinese Material, Anhui University of Chinese Medicine, Hefei 230031, PR China. Electronic address: wnhefei@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230031, PR China; Anhui Key Laboratory of Modernized Chinese Material, Anhui University of Chinese Medicine, Hefei 230031, PR China.
authors.forename: Yafan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei 230031, PR China; Anhui Key Laboratory of Modernized Chinese Material, Anhui University of Chinese Medicine, Hefei 230031, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei 230031, PR China; Anhui Key Laboratory of Modernized Chinese Material, Anhui University of Chinese Medicine, Hefei 230031, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei 230031, PR China; Anhui Key Laboratory of Modernized Chinese Material, Anhui University of Chinese Medicine, Hefei 230031, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei 230031, PR China; Anhui Key Laboratory of Modernized Chinese Material, Anhui University of Chinese Medicine, Hefei 230031, PR China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D065096:Calcium Chelating Agents / Q000494:pharmacology*; D003516:Cycloparaffins / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D000975:Antioxidants; D065096:Calcium Chelating Agents; D003516:Cycloparaffins; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002118:Calcium; C031021:muscone
keywords: Ca(2+); CaMKII; Muscone; PC12 cells; ROS