PI3K-autophagy Pathway Mediates The Secretion Of IL-8in H9C2Rat Cardiomyocytes Induced By Apelin-13

Aims The objective of this study was to investigate the role of apelin-13in thesecretion of IL-8in H9c2cardiomyocytes and to find the molecular mechanism ofPI3K-autophagy pathway mediates the secretion of IL-8in H9c2cardiomyocytesinduced by apelin-13.Methods1. The relationship of APJ and interleukin-8receptor CXCR was predicted bysequence alignment;2. The level of IL-8in H9c2cardiomyocytes culture supernatant was detectedby ELISA;3. The expression of APJ, LC3-Ⅱ/Ⅰ, Beclin1and the phosphorylation of PI3K,Akt, ERK1/2were detected by Western Blot;4. The level of LDH and AST in H9c2cardiomyocytes culture supernatant weredetected by automatic biochemical detector.Results1.APJ has the high homology with CXCR;2.The H9c2cardiomyocytes can produce IL-8; Apelin-13promotes the secretionof IL-8from H9c2cardiomyocytes and reach the peaks at0.01μM and a plateau aftersix hours; After interfer the expression of APJ, the secretion of IL-8induced byapelin-13is inhibited;3.Apelin-13increases the phosphorylation of PI3K、Akt、ERK1/2in H9c2cardiomyocytes; 4.PI3K inhibitor LY294002(25μM), Akt inhibitor1701-1(10μM) and ERK1/2inhibitor PD98059(10μM) can significantly inhibit the secretion of IL-8induced byapelin-13in H9c2cardiomyocytes;5.Apelin-13increases the expression of LC3-II/I and Beclin1in dose and timedependent ways in H9c2cardiomyocytes;6.PI3K inhibitor LY294002(25μM) and Akt inhibitor1701-1(10μM) cansignificantly inhibit the increase of LC3-II/I induced by apelin-13in H9c2cardiomyocytes;7.Autophagy inhibitor3-MA(5mM) can significantly inhibit the secretion of IL-8induced by apelin-13in H9c2cardiomyocytes;8.Apelin-13prevents the secretion of LDH and AST from H9c2ratcardiomyocytes.Conclusion These findings show that apelin-13promotes the secretion of IL-8fromH9c2rat cardiomyocytes mediated by PI3K-autophagy pathway.