Role of oxidative stress in the increased activation of signal transducers and activators of transcription-3 in the fatty livers of obese Zucker rats.
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.
Dikdan
George S
GS
Departments of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
Saba
Salim C
SC
Dela Torre
Andrew N
AN
Roth
Jonathan
J
Wang
Shulun
S
Koneru
Baburao
B
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011924:Rats, Zucker; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology; D024502:alpha-Tocopherol / Q000494:pharmacology
D000975:Antioxidants; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D015534:Trans-Activators; D024502:alpha-Tocopherol