Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes
- Authors
- Hwang, Hwan-Jin; Jung, Tae Woo; Ryu, Ja Young; Hong, Ho Cheol; Choi, Hae Yoon; Seo, Ji A.; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin
- Issue Date
- 5-7월-2014
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Dipeptidyl peptidase-IV inhibitors; Apoptosis; Inflammation; Cardiomyocytes
- Citation
- MOLECULAR AND CELLULAR ENDOCRINOLOGY, v.392, no.1-2, pp.1 - 7
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR AND CELLULAR ENDOCRINOLOGY
- Volume
- 392
- Number
- 1-2
- Start Page
- 1
- End Page
- 7
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/97977
- DOI
- 10.1016/j.mce.2014.04.017
- ISSN
- 0303-7207
- Abstract
- The direct effects of dipeptidyl peptidase-IV (DPP-IV) inhibitors on endoplasmic reticulum (ER) stress-induced apoptosis and inflammation in cardiomyocytes have not been elucidated. H9c2 cell viability, which was reduced by tunicamycin, was increased after DPP-IV inhibitor gemigliptin treatment. Gemigliptin significantly decreased the tunicamycin-mediated increase in glucose regulated protein 78 (GRP78) expression and ER stress-mediated signaling molecules such as protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C-EBP homologous protein (CHOP) and inositol-requiring enzyme 1 alpha (IRE1 alpha)/c-Jun N-terminal kinase (JNK)-p38. Furthermore, gemigliptin effectively induced Akt phosphorylation in a dose-dependent manner. Using flow cytometry and Hoechst staining, we showed that treatment with Akt inhibitor significantly blocked the anti-apoptotic effects mediated by gemigliptin. The reduction in tunicamycin-induced GRP78 level and PERK/CHOP pathway activity by gemigliptin was reversed after treatment with Akt inhibitor. In conclusion, gemigliptin effectively inhibited ER stress-induced apoptosis and inflammation in cardiomyocytes via Akt/PERK/CHOP and IRE1 alpha/JNK-p38 pathways, suggesting its direct protective role in cardiovascular diseases. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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