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  • Attenuating oxygen-glucose deprivation-caused autophagosome accumulation may be involved in sevoflurane postconditioning-induced protection in human neuron-like cells.

Attenuating oxygen-glucose deprivation-caused autophagosome accumulation may be involved in sevoflurane postconditioning-induced protection in human neuron-like cells.

European journal of pharmacology (2019-02-03)
Aobing Cheng, Yang Lu, Qiaobing Huang, Zhiyi Zuo
要旨

Application of the commonly used volatile anesthetic sevoflurane after brain ischemia (sevoflurane postconditioning) attenuates ischemic brain injury. It is not known whether autophagy plays a role in this sevoflurane postconditioning-induced neuroprotection. Human SH-SY5Y cells were induced to become neuron-like cells. These cells were subjected to 1 h oxygen-glucose deprivation (OGD) and then exposed to sevoflurane for 1 h. Chloroquine, an inhibitor of autolysosomes, rapamycin, an autophagy inducer, or 3-methyladenine (3-MA), an autophagy inhibitor, were incubated with cells during OGD and sevoflurane exposure. OGD and the subsequent simulated reperfusion increased lactate dehydrogenase (LDH) release from the cells. This increase was dose-dependent inhibited by sevoflurane postconditioning. OGD increased the ratio of microtubule-associated protein 1 light chain 3 (LC3) II to LC3I and the expression of beclin-1 and p62. These increases were attenuated by sevoflurane. Sevoflurane alone did not have any effects on the expression of p62, beclin-1 and the ratio of LC3II to LC3I. Sevoflurane also enhanced the co-location of autophagosomes and lysosomes. Chloroquine increased the ratio of LC3II to LC3I, p62 and LDH release in cells subjected to OGD. Sevoflurane postconditioning attenuated OGD-induced inactivation of Akt and mechanistic target of rapamycin (mTOR). Inducing autophagosome generation by rapamycin attenuated sevoflurane postconditioning-reduced LDH release. Inhibition of autophagosome generation by 3-MA decreased OGD-induced LDH release. These results suggest that OGD increase autophagosome accumulation via increased formation of autophagosomes and reduced autophagosome clearance and that attenuation of OGD-induced autophagosome accumulation may contribute to sevoflurane postconditioning-induced cell protection.

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Sigma-Aldrich
レチノイン酸, ≥98% (HPLC), powder
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プロテアーゼインヒビターカクテル粉末, for general use, lyophilized powder
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クロロキン 二リン酸塩, powder or crystals, 98.5-101.0% (EP)
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ラパマイシン Streptomyces hygroscopicus由来, ≥95% (HPLC), powder
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3-メチルアデニン, autophagy inhibitor
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L-(−)-グルコース, ≥99%