PMID- 18330685
OWN - NLM
STAT- MEDLINE
DCOM- 20080703
LR  - 20211020
IS  - 0360-3997 (Print)
IS  - 0360-3997 (Linking)
VI  - 31
IP  - 3
DP  - 2008 Jun
TI  - SOCS-1 inhibits TNF-alpha-induced cardiomyocyte apoptosis via ERK1/2 pathway 
      activation.
PG  - 180-8
LID - 10.1007/s10753-008-9063-5 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in 
      mitogen-activated protein kinase (MAPK) signaling pathways, contributes to the 
      pathogenesis of cardiovascular diseases. Recently, suppressor of cytokine 
      signaling-1 (SOCS-1) has been shown to modulate responses to TNF-alpha. However, 
      whether SOCS-1 suppresses TNF-alpha-dependent apoptotic processes in 
      cardiomyocytes and whether MAPK pathways mediate this effect have not been 
      clearly elucidated. This study was carried out to define the role of SOCS-1 on 
      TNF-alpha-induced apoptosis in neonatal rat cardiomyocytes and to investigate the 
      signal pathways involved. Exposure to TNF-alpha (10 ng/ml for 24 h) significantly 
      increased the number of apoptotic cells, the activity of caspase-8 and caspase-3, 
      and the Bax/Bcl-xl ratio. In contrast, adenovirus-mediated gene transfer of 
      SOCS-1 reversed the pro-apoptotic effect of TNF-alpha. Additionally, 
      preincubation of cardiomyocytes with the extracellular signal-regulated kinase-1 
      and -2 (ERK1/2) inhibitor PD98059 attenuated the protective effect of SOCS-1, but 
      the p38-MAPK inhibitor SB203580 and the c-Jun amino-terminal kinase (JNK) 
      inhibitor SP600125 had no effect. Furthermore, the TNF-alpha-induced decrease in 
      the phosphorylation of ERK1/2 was abolished by overexpression of SOCS-1. These 
      findings suggest that SOCS-1 prevents TNF-alpha-induced apoptosis in cardiac 
      myocytes via ERK1/2 pathway activation.
FAU - Yan, Ling
AU  - Yan L
AD  - Department of Cardiology, Renmin Hospital of Wuhan University School of Medicine, 
      238 JieFang Road, Wuchang, Wuhan 430060, People's Republic of China.
FAU - Tang, Qizhu
AU  - Tang Q
FAU - Shen, Difei
AU  - Shen D
FAU - Peng, Sheng
AU  - Peng S
FAU - Zheng, Qian
AU  - Zheng Q
FAU - Guo, Haipeng
AU  - Guo H
FAU - Jiang, Ming
AU  - Jiang M
FAU - Deng, Wei
AU  - Deng W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080311
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Bax protein, rat)
RN  - 0 (Bcl2l1 protein, rat)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (bcl-X Protein)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Casp8 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - *Apoptosis/drug effects
MH  - Caspase 3/metabolism
MH  - Caspase 8/metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism
MH  - Myocytes, Cardiac/drug effects/enzymology/*metabolism/pathology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Proteins/metabolism
MH  - *Signal Transduction/drug effects
MH  - Suppressor of Cytokine Signaling Proteins/genetics/*metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - bcl-2-Associated X Protein/metabolism
MH  - bcl-X Protein/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2008/03/12 09:00
MHDA- 2008/07/04 09:00
CRDT- 2008/03/12 09:00
PHST- 2008/01/09 00:00 [received]
PHST- 2008/02/08 00:00 [accepted]
PHST- 2008/03/12 09:00 [pubmed]
PHST- 2008/07/04 09:00 [medline]
PHST- 2008/03/12 09:00 [entrez]
AID - 10.1007/s10753-008-9063-5 [doi]
PST - ppublish
SO  - Inflammation. 2008 Jun;31(3):180-8. doi: 10.1007/s10753-008-9063-5. Epub 2008 Mar 
      11.