PMID- 22898050
OWN - NLM
STAT- MEDLINE
DCOM- 20130118
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 425
IP  - 4
DP  - 2012 Sep 7
TI  - Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth 
      muscle cells.
PG  - 866-72
LID - 10.1016/j.bbrc.2012.07.165 [doi]
AB  - Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular 
      smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the 
      inflammatory response and migrate to the injured endothelium during the 
      progression of atherosclerosis. Activation of AMP activated protein kinase 
      (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the 
      inflammatory response. However, how AMPK regulates the inflammatory response is 
      poorly understood. To identify the mechanism of this response, we focused on 
      phosphatase and tensin homolog (PTEN), which is a negative regulator of 
      inflammation. We investigated that activation of AMPK-induced PTEN expression and 
      suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. 
      We treated with the well-known AMPK activator metformin to induce PTEN 
      expression. PTEN was induced by metformin (2mM) and inhibited by compound C (10 
      muM) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-alpha) was used to induce 
      inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, 
      inducible nitric oxide synthase (iNOS) expression, and activation of nuclear 
      factor (NF)-kappaB. Metformin suppressed COX-2 and iNOS mRNA and protein expression 
      dose dependently. Treatment with compound C and bpv (pic) in the presence of 
      metformin, iNOS and COX-2 protein expression increased. NF-kappaB activation 
      decreased in response to metformin and was restored by inhibiting AMPK and PTEN. 
      Inhibiting AMPK and PTEN restored ROS levels stimulated with TNF-alpha. Taken 
      together, PTEN could be a possible downstream regulator of AMPK, and the 
      AMPK-PTEN pathway might be important in the regulation of the inflammatory 
      response in VSMCs.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Kim, Sun Ae
AU  - Kim SA
AD  - Department of Pharmacology, Aging-Associated Vascular Disease Research Center, 
      College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
FAU - Choi, Hyoung Chul
AU  - Choi HC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120807
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Animals
MH  - Cells, Cultured
MH  - Hypoglycemic Agents/*pharmacology
MH  - Inflammation/*enzymology
MH  - Male
MH  - Metformin/*pharmacology
MH  - Muscle, Smooth, Vascular/*drug effects/enzymology
MH  - Myocytes, Smooth Muscle/*drug effects/enzymology
MH  - PTEN Phosphohydrolase/genetics/*metabolism
MH  - Protein Kinases/genetics/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2012/08/18 06:00
MHDA- 2013/01/19 06:00
CRDT- 2012/08/18 06:00
PHST- 2012/07/24 00:00 [received]
PHST- 2012/07/31 00:00 [accepted]
PHST- 2012/08/18 06:00 [entrez]
PHST- 2012/08/18 06:00 [pubmed]
PHST- 2013/01/19 06:00 [medline]
AID - S0006-291X(12)01496-9 [pii]
AID - 10.1016/j.bbrc.2012.07.165 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Sep 7;425(4):866-72. doi: 
      10.1016/j.bbrc.2012.07.165. Epub 2012 Aug 7.