Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes

Hwan Jin Hwang, Tae Woo Jung, Ja Young Ryu, Ho Cheol Hong, Hae Yoon Choi, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dong Seop Choi, Sei-Hyun Baik, Hye-Jin Yoo

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 languageEnglish
Pages (from-to)1-7
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume392
Issue number1-2
DOIs
Publication statusPublished - 2014 Jul 5

Fingerprint

Tunicamycin
Endoplasmic Reticulum Stress
Cardiac Myocytes
Transcription Factor CHOP
Apoptosis
Inflammation
Mitogen-Activated Protein Kinase 8
Dipeptidyl-Peptidase IV Inhibitors
Inositol
Phosphorylation
Flow cytometry
MAP Kinase Signaling System
Enzymes
Endoplasmic Reticulum
Protein Kinases
LC15-0444
Cell Survival
Flow Cytometry
Cardiovascular Diseases
Cells

Keywords

  • Apoptosis
  • Cardiomyocytes
  • Dipeptidyl peptidase-IV inhibitors
  • Inflammation

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry
  • Medicine(all)

Cite this

Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes. / 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.

In: Molecular and Cellular Endocrinology, Vol. 392, No. 1-2, 05.07.2014, p. 1-7.

Research output: Contribution to journalArticle

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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.",
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