Role of MAPK phosphatase-1 in the induction of monocyte chemoattractant protein-1 during the course of adipocyte hypertrophy

被引:78
|
作者
Ito, Ayaka
Suganami, Takayoshi
Miyamot, Yoshihiro
Yoshimasa, Yasunao
Takeya, Motohiro
Kamei, Yasutomi
Ogawa, Yoshihiro
机构
[1] Tokyo Med & Dent Univ, Med Res Inst, Chiyoda Ku, Dept Mol Med & Metab, Tokyo 1010062, Japan
[2] Tokyo Med & Dent Univ, Med Res Inst, Chiyoda Ku, Ctr Excellence Program Frontier Res Mol Destruct, Tokyo 1010062, Japan
[3] Natl Cardiovasc Ctr Hosp & Res Inst, Dept Med, Div Atherosclerosis & Diabet, Osaka 5600005, Japan
[4] Kumamoto Univ, Grad Sch Med Sci, Dept Cell Pathol, Kumamoto 8608556, Japan
关键词
D O I
10.1074/jbc.M701549200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Monocyte chemoattractant protein-1 ( MCP-1), an important chemokine whose expression is increased during the course of obesity, plays a role in macrophage infiltration into obese adipose tissue. This study was designed to elucidate the role of mitogen-activated protein kinase ( MAPK) phosphatase-1 ( MKP-1) in the induction of MCP-1 during the course of adipocyte hypertrophy. We examined the time course of MKP-1 and MCP-1 mRNA expression and extracellular signal-regulated kinase ( ERK) phosphorylation in the adipose tissue from mice rendered mildly obese by a short term high fat diet. We also studied the role of MKP-1 in the induction of MCP-1 in 3T3-L1 adipocytes during the course of adipocyte hypertrophy. MCP-1 mRNA expression was increased, followed by ERK activation and down-regulation of MKP-1, an inducible dual specificity phosphatase to inactivate ERK, in the adipose tissue at the early stage of obesity induced by a short term high fat diet, when macrophages are not infiltrated. Down-regulation of MKP-1 preceded ERK activation and increased production of MCP-1 in 3T3-L1 adipocytes in vitro during the course of adipocyte hypertrophy. Adenovirus-mediated restoration of MKP-1 in hypertrophied 3T3-L1 adipocytes reduced the otherwise increased ERK phosphorylation, thereby leading to the significant reduction of MCP-1 mRNA expression. This study provides evidence that the down-regulation of MKP-1 is critical for increased production of MCP-1 during the course of adipocyte hypertrophy.
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收藏
页码:25445 / 25452
页数:8
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