title: Mitigation of H2O2-induced autophagic cell death by propofol in H9c2 cardiomyocytes.
abstract: Autophagy, a self-eating process, is responsible for degradation of long-lived proteins and damaged cellular proteins/organelles. Double-membrane autophagosomes, formed during the process, engulf proteins/organelles and fuse with lysosomes to degrade the contents. It is important to maintain cell homeostasis and many physiological processes including cellular responses to oxidative stress. Oxidative stress induced by myocardial infarction is a major factor of heart failures. In this study, we examined how propofol modulates hydrogen peroxide (H(2)O(2))-induced autophagic cell death in H9c2 cardiomyocytes. H(2)O(2) dramatically induced cell death, which was similarly reduced in the presence of either propofol or autophagy inhibitors (e.g., wortmannin), suggesting that propofol has a protective effect in H(2)O(2)-induced autophagic cell death. Acidic autophagic vacuoles were elevated in H(2)O(2)-treated H9c2 cells, but they were largely decreased in the presence of propofol. Furthermore, many autophagy-related proteins such as LC3-II, ATG proteins, p62, AMPK, and JNK were activated in H(2)O(2)-treated H9c2 cells and were significantly deactivated in the presence of propofol. These results show that propofol regulates oxidative stress-induced autophagic cell death in cardiomyocytes. We further suggest that propofol can act as a cardioprotectant in heart diseases.
authors: Department of Biochemistry, Gyeongsang National University School of Medicine, Jinju, Republic of Korea 660-751.
authors: Ji Hye
authors: JH
authors: Ha
authors: Hae Sook
authors: HS
authors: Noh
authors: Il Woo
authors: IW
authors: Shin
authors: Jong Ryeal
authors: JR
authors: Hahm
authors: Deok Ryong
authors: DR
authors: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D053612:Janus Kinases / Q000187:drug effects / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D055372:AMP-Activated Protein Kinases; D000730:Androstadienes; D002316:Cardiotonic Agents; D006861:Hydrogen Peroxide; D053612:Janus Kinases; D008869:Microtubule-Associated Proteins; D015742:Propofol; D000077191:Wortmannin; C526109:Anxa3 protein, rat