Document Detail


Role of oxidative stress in the increased activation of signal transducers and activators of transcription-3 in the fatty livers of obese Zucker rats.
MedLine Citation:
PMID:  15349118     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Fatty livers have chronic oxidative stress, which could activate several transcription factors. We hypothesized that fatty livers of obese rats have increased activation of signal transducers and activators of transcription-1 and transcription-3 (Stat-1 and Stat-3) and that tocopherol treatment will decrease Stat activation. METHODS: Obese (Ob) and lean (Ln) Zucker rats with or without tocopherol treatment were used. Western blots of liver nuclear and cytoplasmic extracts to assess phosphorylated and total Stat-3 and tyrosine kinases Jak-2 and Tyk-2, immunohistochemistry to assess distribution of phosphoStat-3, and gel shift assays to assess Stat and nuclear factor kappa B binding were performed. Interleukin-6 serum levels and hepatic transcripts were determined by immunoassay and reverse polymerase chain reaction with Southern blotting, respectively. RESULTS: Livers of Ob animals had increased nuclear phosphoStat-3, decreased cytoplasmic Stat-3, and increased Stat-3 binding. Serum interleukin-6 was not measurable in either Ob or Ln animals and hepatic transcript levels were not significantly different. Tocopherol administration decreased nuclear phosphoStat-3, increased cytoplasmic Stat-3, and decreased Stat-3 binding activity. CONCLUSIONS: Chronic oxidative stress in fatty livers is associated with increased Stat-3 activation and decreased cytosolic Stat-3. Tocopherol treatment decreases Stat-3 activation and increases cytosolic Stat-3. Tocopherol-induced changes in Stat-3 may play a role in its beneficial effects in hepatic ischemia in fatty livers.
Authors:
George S Dikdan; Salim C Saba; Andrew N Dela Torre; Jonathan Roth; Shulun Wang; Baburao Koneru
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Surgery     Volume:  136     ISSN:  0039-6060     ISO Abbreviation:  Surgery     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-06     Completed Date:  2004-10-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  677-85     Citation Subset:  AIM; IM    
Affiliation:
Departments of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
DNA-Binding Proteins / drug effects,  metabolism*
Fatty Liver / metabolism*
Interleukin-6 / metabolism
Models, Animal
NF-kappa B / metabolism
Oxidative Stress / drug effects*,  physiology
Rats
Rats, Zucker
STAT1 Transcription Factor
STAT3 Transcription Factor
Signal Transduction / drug effects*,  physiology
Trans-Activators / drug effects,  metabolism*
Transcriptional Activation / drug effects*,  physiology
alpha-Tocopherol / pharmacology
Chemical
Reg. No./Substance:
0/Antioxidants; 0/DNA-Binding Proteins; 0/Interleukin-6; 0/NF-kappa B; 0/STAT1 Transcription Factor; 0/STAT3 Transcription Factor; 0/Stat1 protein, rat; 0/Stat3 protein, rat; 0/Trans-Activators; 59-02-9/alpha-Tocopherol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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