ECE2022 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (202 abstracts)
The role of empagliflozin in palmitate-induced ER stress and apoptosis in H9C2 cells
Jae Yeop Jeong 1 , Sung-E Choi 2 , Min Woo Song 1 , Suck Ho Park 2 , Yup Kang 2 , Tae Ho Kim 3 , So-Yeon Ahn 4 , Hae Jin Kim 1 , Seung jin Han 1 , Ja Young Jeon 1 , Nami Lee 1 , Dae Jung Kim 1 & Kwan-Woo Lee 1
1Ajou University School of Medicine, Department of Endocrinology and Metabolism, Suwon, Rep. of South Korea; 2Ajou University School of Medicine, Department of Physiology, Suwon, Rep. of South Korea; 3Seoul Medical Center, Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul, Rep. of South Korea; 4Busan Bumin Hospital, Division of Endocrinology and Metabolism, Department of Internal Medicine, Busan, Rep. of South Korea
Aim/hypotheses: Ectopic lipid accumulation in the heart contributes to the abnormal function of the heart and to the death of cardiomyocytes. Saturated FFA is one of the most important causes of death in cardiomyocytes. Although empagliflozin has been reported to be beneficial for people with diabetic complications and/or CVD, it has not been confirmed as to how it affects cardiomyocytes death by FFA. This study was designed to evaluate the protective effects of SGLT2 inhibitor on palmitate-induced ER-stress and apoptosis in cardiomyocytes.
Methods: We used differentiated H9C2 cells as cardiomyocytes and palmitate as a saturated fatty acid. To clarify the effects of empagliflozin on apoptosis, free fatty acid was treated with or without empagliflozin in cardiomyocytes and several stress signaling pathways were measured, such as inflammation, endoplasmic reticulum (ER)-stress, and insulin signaling using immunoblotting. Inflammation and cardiac metabolism were analyzed in several related genes. Cardiomyocyte apoptosis was detected using DNA fragmentations assay and immunoblotting using cleaved caspase 3 antibody. DAPI staining was also performed.
Results: Palmitate stimulated increment of ROS (reactive oxygen species) and ER-stress markers such as phospho-eIF2a, CHOP, and phospho-JNK. In addition, cleaved caspase3 and DNA fragmentation was induced by treatment of palmitate. Interestingly, empagliflozin significantly decreased expression levels of ER-stress markers (including phospho-eIF2α, CHOP, and phospho-JNK [Jun N-terminal kinases]) in PA-treated cells. Empagliflozin significantly decreased the activity of cleaved caspase-3 (a well-known apoptotic induced molecule) and DNA fragmentation. To investigate the protective molecular mechanism of empagliflozin, we measured AMPK activation and upstream signal pathways. Empagliflozin significantly stimulated phospho-CAMKK2 and phospho-AMPK. In addition, phosphorylation of acetyl-CoA carboxylase, target protein of AMPK, was also activated by treatment of empagliflozin. But, LKB did not change. Beneficial effects of empagliflozin was abolished by compound C.
Conclusions/interpretation: This data suggests SGLT2 inhibitors protect palmitate induced cardiomyocytes, ER-stress, and apoptosis. Therefore, attempts to use treatment of SGLT2 inhibitor might be a useful strategy for preventing diabetes associated ventricular remodeling and diabetic cardiac complication.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more