PMID- 23376721
OWN - NLM
STAT- MEDLINE
DCOM- 20130903
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 432
IP  - 2
DP  - 2013 Mar 8
TI  - Simvastatin inhibits ox-LDL-induced inflammatory adipokines secretion via 
      amelioration of ER stress in 3T3-L1 adipocyte.
PG  - 365-9
LID - S0006-291X(13)00184-8 [pii]
LID - 10.1016/j.bbrc.2013.01.094 [doi]
AB  - Adipocytes behave as a rich source of pro-inflammatory cytokines including tumor 
      necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP-1). 
      Endoplasmic reticulum (ER) stress in adipocytes can alter adipokines secretion 
      and induce inflammation. The aim of this study is to evaluate the effect of 
      simvastatin on the ox-LDL-induced ER stress and expression and secretion of TNF-alpha 
      and MCP-1 in 3T3-L1 adipocytes. Differentiated adipocytes were treated with 
      various concentrations of ox-LDL (0-100 mug/ml) for 24h with or without 
      simvastatin pre-treatment. The protein expressions of ER stress markers, 
      glucose-regulated protein 78 (GRP78) and C/EBP homology protein (CHOP), were 
      determined by Western blot analysis. The mRNA expressions of TNF-alpha and MCP-1 were 
      measured by real-time PCR. The protein release of TNF-alpha and MCP-1 in culture 
      medium were evaluated by ELISA. Ox-LDL treatment led to significant up-regulation 
      of GRP78 and CHOP in dose-dependent manner. The expressions of TNF-alpha and MCP-1 
      were dose-dependently increased at mRNA and protein levels after ox-LDL 
      intervention. The effects of ox-LDL on adipocytes were abolished by pre-treatment 
      with 4-phenylbutyrate (4-PBA), a chemical chaperone known to ameliorate ER 
      stress. Simvastatin could inhibit ox-LDL-induced ER stress and reduce the 
      expression of TNF-alpha and MCP-1 at mRNA and protien level in dose dependent manner. 
      In conclusion, ox-LDL can stimulate the expression and secretion of TNF-alpha and 
      MCP-1 through its activation of ER stress in adipocytes. Simvastatin might exert 
      direct anti-inflammatory effects in adipocytes through amelioration of ER stress.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Wu, Zhi-hong
AU  - Wu ZH
AD  - Department of Cardiology, The Second Xiangya Hospital of Central South 
      University, Middle Ren-Min Road No. 139, Changsha, Hunan 410011, PR China.
FAU - Chen, Ya-qin
AU  - Chen YQ
FAU - Zhao, Shui-ping
AU  - Zhao SP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130131
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adipokines)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (oxidized low density lipoprotein)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipokines/*antagonists & inhibitors/metabolism
MH  - Animals
MH  - Chemokine CCL2/metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Hypolipidemic Agents/*pharmacology
MH  - Lipoproteins, LDL/*metabolism/pharmacology
MH  - Mice
MH  - Simvastatin/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2013/02/05 06:00
MHDA- 2013/09/04 06:00
CRDT- 2013/02/05 06:00
PHST- 2013/01/11 00:00 [received]
PHST- 2013/01/24 00:00 [accepted]
PHST- 2013/02/05 06:00 [entrez]
PHST- 2013/02/05 06:00 [pubmed]
PHST- 2013/09/04 06:00 [medline]
AID - S0006-291X(13)00184-8 [pii]
AID - 10.1016/j.bbrc.2013.01.094 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2013 Mar 8;432(2):365-9. doi: 
      10.1016/j.bbrc.2013.01.094. Epub 2013 Jan 31.