Protective effect of cholecystokinin octapeptide on angiotensin II‐induced apoptosis in H9c2 cardiomyoblast cells. Issue 7 (30th December 2019)

• Record Type: Journal Article
• Authors: Wang, Can; Yu, Huan; Wei, Limu; Zhang, Jingqi; Hong, Mingyang; Chen, Lin; Dong, Xiaoying; Fu, Lu
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 7(2020)
• Page Start: 3560
• Page End: 3569
• Publication Date: 2019-12-30
• Subjects: angiotensin II -- apoptosis -- cardiomyoblast cells -- PI3K/Akt -- sulfated cholecystokinin octapeptide; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29639
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Cholecystokinin (CCK) and its receptors are expressed in mammalian cardiomyocytes and are involved in cardiovascular system regulation; however, the exact effect and underlying mechanism of CCK in cardiomyocyte apoptosis remain to be elucidated. We examined whether sulfated CCK octapeptide (CCK‐8) protects H9c2 cardiomyoblast cells against angiotensin II (Ang II)‐induced apoptosis. The H9c2 cardiomyoblasts were subjected to Ang II with or without CCK‐8 and the viability and apoptotic rate were detected using a Cell Counting Kit‐8 assay, Hoechst 33342 staining, terminal deoxyribonucleotide transferase‐mediated nick‐end labeling assays, and flow cytometry. In addition, specific antiapoptotic mechanisms of CCK‐8 were investigated using specific CCK1 (Devazepide) or CCK2 (L365260) receptor antagonists, or the PI3K inhibitor LY294002. The expression of CCK, CCK1 receptor, CCK2 receptor, Akt, p‐Akt, Bad, p‐Bad, Bax, Bcl‐2, and caspase‐3 were detected by Western blot analysis and real‐time polymerase chain reaction. We found that CCK and its receptor messenger RNA (mRNA) and protein are expressed in H9c2 cardiomyoblasts. Ang II‐induced increased levels of CCK mRNA and protein expression and decreased levels of CCK1 receptor protein and mRNA. Pretreatment of CCK‐8 attenuated Ang II‐induced cell toxicity and apoptosis. In addition, pretreatment of H9c2 cells with CCK‐8 markedly induced expression of p‐Akt, p‐bad, and Bcl‐2 and decreased the expression levels of Bax and caspase‐3. The protective effects of CCK‐8 were partly abolished by Devazepide or LY294002. Our results suggest that CCK‐8 protects H9c2 cardiomyoblasts from Ang II‐induced apoptosis partly via activation of the CCK1 receptor and the phosphatidyqinositol‐3 kinase/protein kinase B (PI3K/Akt) signaling pathway. Abstract : 1. Cholecystokinin (CCK) and its receptors are expressed in H9c2 cardiomyoblast cell. 2. CCK and CCK‐1 receptor express levels are changed with angiotensin II (Ang II) stimulation. 3. CCK‐8s antagonizes Ang II‐induced apoptosis of H9C2 cells via the activation CCK‐1 receptor and PI3K/Akt pathway.