Document Detail


Involvement of the JAK-STAT pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage RAW 264 cells.
MedLine Citation:
PMID:  20564237     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20 min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death.
Authors:
Sumio Akifusa; Noriaki Kamio; Yoshihiro Shimazaki; Noboru Yamaguchi; Kazuaki Nonaka; Yoshihisa Yamashita
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  111     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-27     Completed Date:  2011-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  597-606     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
Affiliation:
Faculty of Dental Science, Kyushu University, Fukuoka, Japan. akifusa@dent.kyushu-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adiponectin / metabolism*
Animals
Apoptosis
Cell Line
Janus Kinases / metabolism*
Macrophages / metabolism*
Mice
Nitric Oxide / metabolism
Phosphorylation
RNA, Messenger / analysis
Reactive Oxygen Species / metabolism*
STAT Transcription Factors / metabolism
Signal Transduction
Suppressor of Cytokine Signaling Proteins / biosynthesis,  genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Adiponectin; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/STAT Transcription Factors; 0/Socs3 protein, mouse; 0/Suppressor of Cytokine Signaling Proteins; 10102-43-9/Nitric Oxide; EC 2.7.10.2/Janus Kinases

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