Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells

Tae Woo Jung, Hwan Jin Hwang, Ho Cheol Hong, Hae Yoon Choi, Hye-Jin Yoo, Sei-Hyun Baik, Kyung Mook Choi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume391
Issue number1-2
DOIs
Publication statusPublished - 2014 Jun 25

Fingerprint

Endoplasmic Reticulum Stress
JNK Mitogen-Activated Protein Kinases
Hep G2 Cells
Triglycerides
Apoptosis
Tunicamycin
Caspase 3
Liver
Obesity
Anisomycin
Protein folding
Phosphorylation
resolvin D1
Protein Folding
Medical problems
Unsaturated Fatty Acids
Endoplasmic Reticulum
Type 2 Diabetes Mellitus
Anti-Inflammatory Agents
Insulin

Keywords

  • C-Jun N-terminal kinase
  • ER stress
  • Non-alcoholic fatty liver
  • Proliferator-activated receptor-γ
  • Resolvin D1

ASJC Scopus subject areas

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

Cite this

Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells. / Jung, Tae Woo; Hwang, Hwan Jin; Hong, Ho Cheol; Choi, Hae Yoon; Yoo, Hye-Jin; Baik, Sei-Hyun; Choi, Kyung Mook.

In: Molecular and Cellular Endocrinology, Vol. 391, No. 1-2, 25.06.2014, p. 30-40.

Research output: Contribution to journalArticle

@article{9a1cbaff4de049168d63a9c872c0626c,
title = "Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells",
abstract = "Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD.",
keywords = "C-Jun N-terminal kinase, ER stress, Non-alcoholic fatty liver, Proliferator-activated receptor-γ, Resolvin D1",
author = "Jung, {Tae Woo} and Hwang, {Hwan Jin} and Hong, {Ho Cheol} and Choi, {Hae Yoon} and Hye-Jin Yoo and Sei-Hyun Baik and Choi, {Kyung Mook}",
year = "2014",
month = "6",
day = "25",
doi = "10.1016/j.mce.2014.04.012",
language = "English",
volume = "391",
pages = "30--40",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells

AU - Jung, Tae Woo

AU - Hwang, Hwan Jin

AU - Hong, Ho Cheol

AU - Choi, Hae Yoon

AU - Yoo, Hye-Jin

AU - Baik, Sei-Hyun

AU - Choi, Kyung Mook

PY - 2014/6/25

Y1 - 2014/6/25

N2 - Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD.

AB - Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD.

KW - C-Jun N-terminal kinase

KW - ER stress

KW - Non-alcoholic fatty liver

KW - Proliferator-activated receptor-γ

KW - Resolvin D1

UR - http://www.scopus.com/inward/record.url?scp=84899853191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899853191&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2014.04.012

DO - 10.1016/j.mce.2014.04.012

M3 - Article

VL - 391

SP - 30

EP - 40

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 1-2

ER -