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
N1 - Funding Information:
This research was supported by a Korea University Grant and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012006363 ) (K.M.C.) and by the Brain Korea 21 Project of the Ministry of Education and Human Resources Development, Republic of Korea (K.M.C. and S.H.B.).
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
U2 - 10.1016/j.mce.2014.04.012
DO - 10.1016/j.mce.2014.04.012
M3 - Article
C2 - 24784707
AN - SCOPUS:84899853191
VL - 391
SP - 30
EP - 40
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -
