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

Authors:
Aobing Cheng
Aobing Cheng
Memorial Sloan Kettering Cancer Center
Yang Lu
Yang Lu
City University of Hong Kong
China
Qiaobing Huang
Qiaobing Huang
Key Lab for Shock and Microcirculation Research of Guangdong
Zhiyi Zuo
Zhiyi Zuo
University of Virginia
United States

Eur J Pharmacol 2019 Apr 30;849:84-95. Epub 2019 Jan 30.

Department of Anesthesiology, University of Virginia, Charlottesville, VA 22901, USA. Electronic address:

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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Source
http://dx.doi.org/10.1016/j.ejphar.2019.01.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414235PMC

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April 2019
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