IL-6 related specificity of haptoglobin gene regulation in the liver of diabetic rats
2007
Аутори:
Ivanović-Matić, SvetlanaBogojević, Desanka
Uskoković, Aleksandra
Arambašić Jovanović, Jelena
Mihailović, Mirjana
Grdović, Nevena
Vidaković, Melita
Dinić, Svetlana
Martinović, Vesna
Petrović, Miodrag
Poznanović, Goran
Grigorov, Ilijana
Тип документа:
Конференцијски прилог (Објављена верзија)
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© SAGE Publications
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Приказ свих података о документуАпстракт:
Haptoglobin (Hp), an acute-phase protein with antioxidant proper- ties, is produced by liver cells primarily in response to IL-6 type cytokines. IL-6 cytokines mediate the induction of the Hp gene by the inducible form of the signal transducer and activator of tran- scription-3 protein (STAT3) and the CAAT/enhancer binding protein beta (C/EBPβ). This study was aimed at revealing the specificity of the IL-6 signal transduction pathways in the regulation of Hp gene expression in different diabetic phases. Diabetes was induced in male Wistar rats by single streptozotocin injection (65 mg/kg body weight). An 8-fold increase in the Hp serum level was observed two weeks after treatment (early phase) by rocket immunoelectrophore- sis. Four end seven weeks after treatment, Hp expression was still elevated but lower than after two weeks. The specificity by which the IL-6-related transcription factors regulate Hp gene transcription in diabetic rats was determined by examining of profiles (Western- immunoblot) and DNA binding activities of STAT3 and C/EBPα and
β isoforms expressed in hepatocytes. DNA-affinity chromatography with the Hp gene hormone responsive element (HRE) revealed per- manent HRE binding of inducible Tyr phosphorylated 91kD STAT3 isoform. C/EBPβ isoforms primarily mediated Hp gene regulation during the early phase of diabetes while C/EBPα was involved after four week of treatment, during progression of the illness. The obtained results suggest that the molecular machinery that mediates Hp gene regulation becomes slightly altered as diabetes progresses probably as the result of an impaired balance between pro- (IL-6) and anti-inflammatory (insulin) mediators.
У:
- Abstracts of the 2nd International Congress on Prediabetes and the Metabolic Syndrome; 2007 Apr 25-28; Barcelona, Spain. SAGE Publications; 2007. (Diabetes and Vascular Disease Research; March; Suppl. 1).