Protection of Dexmedetomidine Against Ischemia/Reperfusion-Induced Apoptotic Insults to Neuronal Cells Occurs Via an Intrinsic Mitochondria-Dependent Pathway

Autor: Shing-Hwa Liu, Ta Liang Chen, Hsiao Chien Tsai, Jui Tai Chen, Gong Jhe Wu, Ruei Ming Chen
Rok vydání: 2017
Předmět:
Zdroj: Journal of Cellular Biochemistry. 118:2635-2644
ISSN: 0730-2312
DOI: 10.1002/jcb.25847
Popis: Dexmedetomidine, an agonist of alpha2-adrenergic receptors, is used for critically ill patients to induce and maintain sedation and analgesia. Brain ischemia/reperfusion (I/R) usually causes severe neuronal injuries to intensive care unit patients. This study was aimed to evaluate the effects of dexmedetomidine on I/R-induced insults to neuronal cells and the possible mechanisms. Treatment of neuro-2a cells with dexmedetomidine did not affect cell viability but could protect against I/R-induced cell death. Separately, the I/R-triggered cell shrinkage, DNA fragmentation, and apoptosis in neuro-2a cells were alleviated by dexmedetomidine. As to the mechanisms, exposure of neuro-2a cells to dexmedetomidine substantially attenuated I/R-induced translocation of Bax protein from the cytosol to mitochondria and reduction in the mitochondrial membrane potential (MMP). Successively, dexmedetomidine decreased cytochrome c release from mitochondria to the cytoplasm and consequent cascade activations of caspases-9, -3, and -6 in I/R-treated neuro-2a cells. Interestingly, downregulating caspase-6 activity synergistically improved dexmedetomidine-induced defense against I/R-induced apoptosis of neuro-2a cells. The dexmedetomidine-involved neuroprotection was further confirmed in the other NB41A3 neuronal cells by significantly attenuating I/R-induced changes in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study has shown the neuroprotective effects of dexmedetomidine against I/R-induced apoptotic insults via an intrinsic Bax-mitochondria-cytochrome c-caspase protease pathway. J. Cell. Biochem. 118: 2635-2644, 2017. © 2016 Wiley Periodicals, Inc.
Databáze: OpenAIRE
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