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Targeting cyclophilin-D by compound 19 protects neuronal cells from oxygen glucose deprivation/re-oxygenation.

ABSTRACT: Oxygen and glucose deprivation (OGD) with re-oxygenation (OGDR) is applied to neuronal cells to mimic ischemia-reperfusion injuries. Activation of cyclophilin D (Cyp-D)-dependent programmed necrosis pathway mediates OGDR-induced neuronal cell damages. Here, we tested the potential effect of Compound 19 (C19), a novel Cyp-D inhibitor, in this process. In both established neuronal cell lines (Neuro-2a and NB41A3 cells) and the primary murine CA1 hippocampal neurons, pretreatment with C19 largely attenuated OGDR-induced cell viability reduction and cell death. Significantly, C19 was ineffective in Cyp-D-silenced Neuro-2a cells. OGDR induced mitochondria-dependent programmed necrosis in neuronal cells. OGDR induced p53 translocation to mitochondria and association with Cyp-D, causing mitochondrial depolarization, cytochrome C release and reactive oxygen species production. Such effects were largely attenuated with pre-treatment of C19. Importantly, C19 was significantly more efficient than other known Cyp-D inhibitors in protecting neuronal cells from OGDR. These results suggest that targeting Cyp-D by C19 protects neuronal cells from OGDR.

SUBMITTER: Zheng J

PROVIDER: S-EPMC5685745 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Targeting cyclophilin-D by compound 19 protects neuronal cells from oxygen glucose deprivation/re-oxygenation.

Zheng Jinyu J Cui Enhui E Yang Haikou H Li Mao M Zhou Jing J Yan Ming M Sun Jian J Tang De-Rong DR

Oncotarget 20171006 52

Oxygen and glucose deprivation (OGD) with re-oxygenation (OGDR) is applied to neuronal cells to mimic ischemia-reperfusion injuries. Activation of cyclophilin D (Cyp-D)-dependent programmed necrosis pathway mediates OGDR-induced neuronal cell damages. Here, we tested the potential effect of Compound 19 (C19), a novel Cyp-D inhibitor, in this process. In both established neuronal cell lines (Neuro-2a and NB41A3 cells) and the primary murine CA1 hippocampal neurons, pretreatment with C19 largely a ...[more]

PMID: 29163824

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Targeting cyclophilin-D by compound 19 protects neuronal cells from oxygen glucose deprivation/re-oxygenation.

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Targeting cyclophilin-D by compound 19 protects neuronal cells from oxygen glucose deprivation/re-oxygenation.

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