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01-12-2017 | Original Paper

Isorhynchophylline Attenuates MPP⁺-Induced Apoptosis Through Endoplasmic Reticulum Stress- and Mitochondria-Dependent Pathways in PC12 Cells: Involvement of Antioxidant Activity

Authors: Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong

Published in: NeuroMolecular Medicine | Issue 4/2017

Abstract

Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson’s disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP⁺)-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP⁺-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP⁺-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway. IRN-mediated attenuation of endoplasmic reticulum modulator caspase-12 activation was abolished by diphenyleneiodonium (DPI) or IRE-1α shRNA, but not by SP600125 or pifithrin-α in MPP⁺-treated PC12 cells. Inhibitions of MPP⁺-induced both cytochrome c release and caspase-9 activation by IRN were blocked by pre-treatment with DPI or pifithrin-α, but not by IRE-1α shRNA. IRN blocks the generation of reactive oxygen species upstream of both ASK1/JNK pathway and IRE1/caspase-12 pathway. Altogether, our in vitro findings suggest that IRN possesses potent neuroprotective activity and may be a potential candidate for the treatment of PD.

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Title: Isorhynchophylline Attenuates MPP+-Induced Apoptosis Through Endoplasmic Reticulum Stress- and Mitochondria-Dependent Pathways in PC12 Cells: Involvement of Antioxidant Activity
Authors: Xiao-Ming Li
Xiao-Jie Zhang
Miao-Xian Dong
Publication date: 01-12-2017
Publisher: Springer US
Published in: NeuroMolecular Medicine / Issue 4/2017
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-017-8462-x

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Isorhynchophylline Attenuates MPP⁺-Induced Apoptosis Through Endoplasmic Reticulum Stress- and Mitochondria-Dependent Pathways in PC12 Cells: Involvement of Antioxidant Activity

Abstract

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