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Propofol Postconditioning Ameliorates Hypoxia/Reoxygenation induced H9c2 Cells Apoptosis and Autophagy via upregulating Forkhead Transcription Factors under Hyperglycemia
Author(s) -
Han Ronghui,
Han Hong,
Xie Xiang,
Chen Hao,
Liu Danyong,
Zhang Liangqing,
Xia Zhengyuan
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08671
Subject(s) - cardioprotection , autophagy , propofol , apoptosis , pharmacology , oxidative stress , foxo1 , hypoxia (environmental) , reperfusion injury , reactive oxygen species , lactate dehydrogenase , medicine , ischemia , chemistry , protein kinase b , oxygen , biochemistry , enzyme , organic chemistry
Administration of propofol, an intravenous anesthetic with antioxidant property, immediately at the onset of post‐ischemic reperfusion (propofol postconditioning, P‐PostC) has been shown to confer cardioprotection against ischemia‐reperfusion injury , while the underlying mechanism remains incompletely understood. Also, whether or not P‐PostC can confer cardioprotection in diabetes or under hyperglycemic condition has yet to be explored. The FoxO transcription factors were reported to play critical roles in promoting cardiomyocyte survival during conditions of oxidative stress through induction of antioxidants and cell survival pathways (J Biol Chem. 2011;286(9):7468–78) and was also involved in hypoxic postconditioning mediated neuroprotection. However, the role of Foxo in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown. We hypothesized that P‐PostC may attenuate hypoxia/reoxygenation (H/R) injury in cardiac origin H9c2 cells by attenuating apoptosis and autophagy through upregulating FoxO1 and FoxO3a under hyperglycemia. Rat heart‐derived H9c2 cells were exposed to high glucose (HG) for 48 hours, then subjected to H/R (composed of 8 hours of hypoxia followed by 12 hours of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol at the onset of reoxygenation. Our data showed that HG with or without H/R decreased cell viability, increased lactate dehydrogenase (LDH) leakage and the production of reactive oxygen species (ROS) in H9c2 cells, all of which were significantly reversed by propofol (P‐PostC), especially at the concentration of 25μM. Moreover, we found that propofol (P25) decreased H9c2 cells apoptosis and autophagy that were associated with increased FoxO1 and FoxO3a expression. The protective effects of propofol (P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a. Taken together, these results indicated that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia. Support or Funding Information Supported by National Natural Science Foundation of China (NSFC) grant (81970247)