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

doi:10.1016/j.mce.2014.04.017

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 journal › Article › peer-review

31 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 language	English
Pages (from-to)	1-7
Number of pages	7
Journal	Molecular and Cellular Endocrinology
Volume	392
Issue number	1-2
DOIs	https://doi.org/10.1016/j.mce.2014.04.017
Publication status	Published - 2014 Jul 5

Bibliographical note

Funding Information:
Dr. S.H. Baik and Dr. K.M. Choi were supported by the Brain Korea 21 Project of the Ministry of Education and Human Resources Development, Republic of Korea ( A102065-1011-1070100 ). Dr. K.M. Choi received support from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012006363 ). Dr. H.J. Yoo was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012R1A1A1005257 ) and by a Korea University grant ( K1325151 ). Gemigliptin was provided by LG Life Sciences Ltd., Seoul, Korea.

Keywords

Apoptosis
Cardiomyocytes
Dipeptidyl peptidase-IV inhibitors
Inflammation

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.mce.2014.04.017

Cite this

Hwang, H. J., Jung, T. W., Ryu, J. Y., Hong, H. C., Choi, H. Y., Seo, J. A., Kim, S. G., Kim, N. H., Choi, K. M., Choi, D. S., Baik, S. H., & Yoo, H. J. (2014). Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes. Molecular and Cellular Endocrinology, 392(1-2), 1-7. https://doi.org/10.1016/j.mce.2014.04.017

Hwang, HJ, Jung, TW, Ryu, JY, Hong, HC, Choi, HY, Seo, JA, Kim, SG, Kim, NH, Choi, KM, Choi, DS, Baik, SH & Yoo, HJ 2014, 'Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes', Molecular and Cellular Endocrinology, vol. 392, no. 1-2, pp. 1-7. https://doi.org/10.1016/j.mce.2014.04.017

@article{96e6ed39ec7f4e70b276dc4b2c6f9801,

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

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.",

keywords = "Apoptosis, Cardiomyocytes, Dipeptidyl peptidase-IV inhibitors, Inflammation",

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

note = "Funding Information: Dr. S.H. Baik and Dr. K.M. Choi were supported by the Brain Korea 21 Project of the Ministry of Education and Human Resources Development, Republic of Korea ( A102065-1011-1070100 ). Dr. K.M. Choi received support from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012006363 ). Dr. H.J. Yoo was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012R1A1A1005257 ) and by a Korea University grant ( K1325151 ). Gemigliptin was provided by LG Life Sciences Ltd., Seoul, Korea.",

year = "2014",

month = jul,

day = "5",

doi = "10.1016/j.mce.2014.04.017",

language = "English",

volume = "392",

pages = "1--7",

journal = "Molecular and Cellular Endocrinology",

issn = "0303-7207",

publisher = "Elsevier Ireland Ltd",

number = "1-2",

}

TY - JOUR

T1 - Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes

AU - Hwang, Hwan Jin

AU - Jung, Tae Woo

AU - Ryu, Ja Young

AU - Hong, Ho Cheol

AU - Choi, Hae Yoon

AU - Seo, Ji A.

AU - Kim, Sin Gon

AU - Kim, Nan Hee

AU - Choi, Kyung Mook

AU - Choi, Dong Seop

AU - Baik, Sei Hyun

AU - Yoo, Hye Jin

N1 - Funding Information: Dr. S.H. Baik and Dr. K.M. Choi were supported by the Brain Korea 21 Project of the Ministry of Education and Human Resources Development, Republic of Korea ( A102065-1011-1070100 ). Dr. K.M. Choi received support from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012006363 ). Dr. H.J. Yoo was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012R1A1A1005257 ) and by a Korea University grant ( K1325151 ). Gemigliptin was provided by LG Life Sciences Ltd., Seoul, Korea.

PY - 2014/7/5

Y1 - 2014/7/5

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cardiomyocytes

KW - Dipeptidyl peptidase-IV inhibitors

KW - Inflammation

UR - http://www.scopus.com/inward/record.url?scp=84901000873&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2014.04.017

DO - 10.1016/j.mce.2014.04.017

M3 - Article

C2 - 24813659

AN - SCOPUS:84901000873

SN - 0303-7207

VL - 392

SP - 1

EP - 7

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 1-2

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this