Globular CTRP9 protects cardiomyocytes from palmitic acid-induced oxidative stress by enhancing autophagic flux
| Autor: | Yuan Guo, Dan Xu, Linmao Lyu, Xiaoyu Zhao, Anju Zuo, Shiyan Ruan, Chengxiang Song, Tingting Li, Na Li, Ji-Ying Chen, Shengyun Lei, Jun Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Autophagosome Cell Survival ATG5 Palmitic Acid Oxidative phosphorylation Toxicology medicine.disease_cause Autophagy-Related Protein 5 03 medical and health sciences 0302 clinical medicine Sequestosome-1 Protein Autophagy medicine Animals Myocyte Myocytes Cardiac RNA Small Interfering Cells Cultured Caspase Membrane Potential Mitochondrial biology Caspase 3 Chemistry General Medicine Rats Cell biology Oxidative Stress 030104 developmental biology Lipotoxicity 030220 oncology & carcinogenesis biology.protein RNA Interference Adiponectin Reactive Oxygen Species Microtubule-Associated Proteins Oxidative stress |
| Zdroj: | Chemico-Biological Interactions. 329:109094 |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2020.109094 |
| Popis: | Background Oxidative stress in cardiac myocytes is an important pathogenesis of cardiac lipotoxicity. Autophagy is a cellular self-digestion process that can selectively remove damaged organelles under oxidative stress, and thus presents a potential therapeutic target against cardiac lipotoxicity. Globular CTRP9 (gCTRP9) is a newly identified adiponectin paralog with established metabolic regulatory properties. The aim of this work is to investigate whether autophagy participates the protection effects of gCTRP9 in neonatal rat cardiac myocytes (NRCMs) under oxidative stress and the underlying mechanism. Results NRCMs were treated with PA of various concentrations for indicated time period. Our results showed that PA enhanced intracellular ROS accumulation, decreased mitochondrial membrane potential (Δψm) and increased activation of caspases 3. These changes suggested lipotoxicity due to excessive PA. In addition, PA was observed to impair autophagic flux in NRCMs and impaired autophagosome clearance induced by PA contributes to cardiomyocyte death. Besides, we found that gCTRP9 increased the ratio of LC3II/I and the expression of ATG5 which was vital to the formation of autophagosomes and decreased the level of P62, suggesting enhanced autophagic flux in the absence or presence of PA. The result was further confirmed by the methods of infection with LC3-mRFP-GFP lentivirus and blockage of autophagosome–lysosome fusion by BafA1. Moreover, gCTRP9 reestablished the loss of mitochondrial membrane potential, suppressed ROS generation, and reduced PA -induced myocyte death. However, the protective effect of gCTRP9 on the cardiac lipotoxicity was partly abolished by blockade of autophagy by autophagy-related 5 (ATG5) siRNA, indicating that the effect of gCTRP9 on cell survival is critically mediated through regulation of autophagy. Conclusion Autophagy induction by gCTRP9 could be utilized as a potential therapeutic strategy against oxidative stress-mediated damage in cardiomyocytes. |
| Databáze: | OpenAIRE |
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