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Propofol Attenuates Hypoxia/Reoxygenation-Induced Apoptosis and Autophagy in HK-2 Cells by Inhibiting JNK Activation

Yonsei Medical Journal 2019년 60권 12호 p.1195 ~ 1202
 ( Wang Huaxin ) - Wuhan University Renmin Hospital Department of Anesthesiology

 ( Peng Xuan ) - Wuhan University Renmin Hospital Department of Anesthesiology
 ( Huang Yayi ) - Wuhan University Renmin Hospital Department of Anesthesiology
 ( Xiao Yeda ) - Wuhan University Renmin Hospital Department of Anesthesiology
 ( Wang Zhuo ) - Wuhan University Renmin Hospital Department of Anesthesiology
 ( Zhan Liying ) - Wuhan University Renmin Hospital Department of Anesthesiology

Abstract


Purpose: The aim of this study was to investigate whether propofol could attenuate hypoxia/reoxygenation-induced apoptosis and autophagy in human renal proximal tubular cells (HK-2) by inhibiting JNK activation.

Materials and Methods: HK-2 cells were treated with or without propofol or JNK inhibitor SP600125 for 1 hour and then subjected to 15 hours of hypoxia and 2 hours of reoxygenation (H/R). Cell viability and LDH release were measured with commercial kits. Cell apoptosis was evaluated by flow cytometry. The expressions of p-JNK, cleaved-caspase-3, Bcl-2, and autophagy markers LC3 and p62 were measured by Western blot or immunofluorescence.

Results: HK-2 cells exposed to H/R insult showed higher cell injury (detected by increased LDH release and decreased cell viability), increased cell apoptosis index and expression of cleaved-caspase-3, a decrease in the expression of Bcl-2 accompanied by increased expression of p-JNK and LC3II, and a decrease in expression of p62. All of these alterations were attenuated by propofol treatment. Similar effects were provoked upon treatment with the JNK inhibitor SP600125. Moreover, the protective effects were more obvious with the combination of propofol and SP600125.

Conclusion: These results suggest that propofol could attenuate hypoxia/reoxygenation induced apoptosis and autophagy in HK-2 cells, probably through inhibiting JNK activation.

키워드

Propofol; HK-2 cells; apoptosis; autophagy
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