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 1α (IRE1α)/c-Jun N-terminal kinase (JNK)-p38. Furthermore, gemigliptin effectively induced A. kt phosphorylation in a dose-dependent manner. Using flow cytometry and Hoechst staining, we showed that treatment with A. kt 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 A. kt inhibitor. In conclusion, gemigliptin effectively inhibited ER stress-induced apoptosis and inflammation in cardiomyocytes via A. kt/PERK/CHOP and IRE1α/JNK-p38 pathways, suggesting its direct protective role in cardiovascular diseases.
Original language | English |
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Pages (from-to) | 1-7 |
Number of pages | 7 |
Journal | Molecular and Cellular Endocrinology |
Volume | 392 |
Issue number | 1-2 |
DOIs | |
Publication status | Published - 2014 Jul 5 |
Keywords
- Apoptosis
- Cardiomyocytes
- Dipeptidyl peptidase-IV inhibitors
- Inflammation
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology