Acute hypoxic preconditioning prevents palmitic acid-induced cardiomyocyte apoptosis via switching metabolic GLUT4-glucose pathway back to CD36-fatty acid dependent.
Metabolic syndrome is a risk factor for the development of cardiovascular diseases. Myocardial cell damage leads to an imbalance of energy metabolism, and many studies have indicated that short-term hypoxia during myocardial cell injury has a protective effect. In our previous animal studies, we found that short-term hypoxia in the heart has a protective effect, but long-term hypoxia increases myocardial cell injury. Palmitic acid (PA)-treated H9c2 cardiomyoblasts and neonatal rat ventricle cardiomyocytes were used to simulate hyperlipidemia model, which suppress cluster of differentiation 36 (CD36) and activate glucose transporter type 4 (GLUT4). We exposed the cells to short- and long-term hypoxia and investigated the protective effects of hypoxic preconditioning on PA-induced lipotoxicity in H9c2 cardiomyoblasts and neonatal rat cardiomyocytes. Preconditioning with short-term hypoxia enhanced both CD36 and GLUT4 metabolism pathway protein levels. Expression levels of phospho-PI3K, phospho-Akt, phospho-AMPK, SIRT1, PGC1α, PPARα, CD36, and CPT1β induced by PA was reversed by short-term hypoxia in a time-dependent manner. PA-induced increased GLUT4 membrane protein level was reduced in the cells exposed to short-term hypoxia and si-PKCζ. Short-term hypoxia, resveratrol and si-PKCζ rescue H9c2 cells from apoptosis induced by PA and switch the metabolic pathway from GLUT4 dependent to CD36 dependent. We demonstrate short-term hypoxic preconditioning as a more efficient way as resveratrol in maintaining the energy metabolism of hearts during hyperlipidemia and can be used as a therapeutic strategy.
['Chen|Yeh-Peng|YP|', 'Kuo|Wei-Wen|WW|', 'Baskaran|Rathinasamy|R|', 'Day|Cecilia-Hsuan|CH|', 'Chen|Ray-Jade|RJ|', 'Wen|Su-Ying|SY|', 'Ho|Tsung-Jung|TJ|', 'Padma|Viswanadha Vijaya|VV|0000-0001-9154-027X', 'Kuo|Chia-Hua|CH|', 'Huang|Chih-Yang|CY|0000-0003-2347-0411']
D000818:Animals D000831:Animals, Newborn D017209:Apoptosis D018955:CD36 Antigens D015687:Cell Hypoxia D002460:Cell Line D004268:DNA-Binding Proteins D005227:Fatty Acids D005947:Glucose D006352:Heart Ventricles D006949:Hyperlipidemias D053858:Metabolic Networks and Pathways D008954:Models, Biological D032383:Myocytes, Cardiac D019308:Palmitic Acid D051381:Rats D014157:Transcription Factors
hypoxia palmitic acid fatty acid metabolism glucose metabolism insulin signaling pathway ischemia