Autophagy Plays A Protective Role In Advanced Glycation End Product Induced Apoptosis In Cardiomyocytes

Background/Aims:To investigate the effect of advanced glycation endproduct-induced autophagy in rat cardiomyocytes and to identify the role of autophagy in advanced glycation end product-induced cell apoptosis.Methods:After cultured rat cardiomyocytes were treated with advanced glycation end products (AGEs), protein expression was detected by western blotting, autophagosomes were observed by electron microscopy, the cell apoptotic rate was determined by flow cytometry, and cell variability was quantified by the MTT assay.Results:After cultured cardiomyocytes were treated with AGEs, the level of autophagy-Associated protein LC3-II was up-regulated and SQSTM1/p62 was down-regulated; the number of autophagosomes was increased. Compared with the control group, the apoptotic rate of cardiomyocytes increased, and the cardiomyocyte viability was decreased in the AGE-treated group. Furthermore, pretreating cells with3-MA, an autophagy inhibitor, could enhance these effects. Treatment with AGEs activated phospho-ERK, phospho-JNK, and phospho-p38/MAPK but inhibited phospho-Akt and phospho-mTOR. Pretreatment with an ERK inhibitor PD98059 or an Akt activator IGF-1 could inhibit AGE-induced autophagy, whereas, pretreatment with P38 inhibitor SP600125 or an Akt activator IGF-1 could inhibit AGEs-induced apoptosis.Conclusion:This experiment treats rats cardiomyocytes as the object, which studied autophagy and apoptosis on the influence of AGEs. AGEs can induce autophagy through the PI3K/AKT/mTOR and ERK signalling pathways and induce apoptosis through the PI3K/AKT/mTOR and p38/MAPK signalling pathways in rat cardiomyocytes. Autophagy plays a protective role in AGE-induced apoptosis in cardiomyocytes.