PMID- 17094942
OWN - NLM
STAT- MEDLINE
DCOM- 20070123
LR  - 20171116
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 351
IP  - 4
DP  - 2006 Dec 29
TI  - Simvastatin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha 
      expression in neonatal rat cardiomyocytes: The role of reactive oxygen species.
PG  - 947-52
AB  - Tumor necrosis factor-alpha (TNF-alpha) is implicated in heart failure and 
      cardiomyocytes themselves can express TNF-alpha. Nevertheless, the mechanisms and 
      regulations of TNF-alpha expression in cardiomyocytes remain poorly understood. 
      The present study was to investigate the effects of simvastatin on TNF-alpha 
      expression in cardiomyocytes and the underlying molecular mechanisms. In neonatal 
      rat cardiomyocytes, RT-PCR and ELISA showed lipopolysaccharide (LPS)-induced 
      TNF-alpha expression was attenuated by simvastatin pretreatment in a 
      dose-dependent manner. The reactive oxygen species (ROS) scavenger 
      N-acetylcysteine and the NADPH oxidase inhibitor diphenyleneiodonium also 
      inhibited the LPS-induced expression of TNF-alpha. 
      Dichlorofluorescein-fluorescence and cytochrome c reduction assay indicated LPS 
      increased ROS generation and NADPH oxidase activity in cardiomyocytes, which were 
      abrogated by simvastatin. Furthermore, similar to LPS, exogenous hydrogen 
      peroxide also increased TNF-alpha secretion, but simvastatin did not 
      significantly affect the hydrogen peroxide-induced TNF-alpha secretion. All the 
      effects of simvastatin as mentioned above were completely reversed by concomitant 
      pretreatment with mevalonate, a key intermediate during cholesterol synthesis. 
      These results suggest that simvastatin attenuates LPS-induced TNF-alpha 
      expression in cardiomyocytes via inhibition of activation of NADPH oxidase and 
      subsequent ROS generation.
FAU - Shang, Fujun
AU  - Shang F
AD  - Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an 710038, PR China.
FAU - Zhao, Lianyou
AU  - Zhao L
FAU - Zheng, Qiangsun
AU  - Zheng Q
FAU - Wang, Jiepin
AU  - Wang J
FAU - Xu, Zhe
AU  - Xu Z
FAU - Liang, Wenbing
AU  - Liang W
FAU - Liu, Hui
AU  - Liu H
FAU - Liu, Shaowei
AU  - Liu S
FAU - Zhang, Lijuan
AU  - Zhang L
LA  - eng
PT  - Journal Article
DEP - 20061102
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Onium Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 6HJ411TU98 (diphenyleneiodonium)
RN  - AGG2FN16EV (Simvastatin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - S5UOB36OCZ (Mevalonic Acid)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Free Radical Scavengers/pharmacology
MH  - Hydrogen Peroxide/pharmacology
MH  - Hypolipidemic Agents/*pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Mevalonic Acid/pharmacology
MH  - Myocytes, Cardiac/*drug effects/metabolism
MH  - NADPH Oxidases/*antagonists & inhibitors
MH  - Onium Compounds/pharmacology
MH  - Rats
MH  - Reactive Oxygen Species/antagonists & inhibitors/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Simvastatin/antagonists & inhibitors/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/genetics/metabolism
EDAT- 2006/11/11 09:00
MHDA- 2007/01/24 09:00
CRDT- 2006/11/11 09:00
PHST- 2006/10/24 00:00 [received]
PHST- 2006/10/25 00:00 [accepted]
PHST- 2006/11/11 09:00 [pubmed]
PHST- 2007/01/24 09:00 [medline]
PHST- 2006/11/11 09:00 [entrez]
AID - S0006-291X(06)02398-9 [pii]
AID - 10.1016/j.bbrc.2006.10.134 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2006 Dec 29;351(4):947-52. doi: 
      10.1016/j.bbrc.2006.10.134. Epub 2006 Nov 2.