title: STAT3/NF-κB interactions determine the level of haptoglobin expression in male rats exposed to dietary restriction and/or acute phase stimuli.
abstract: Haptoglobin is a constitutively expressed protein which is predominantly synthesized in the liver. During the acute-phase (AP) response haptoglobin is upregulated along with other AP proteins. Its upregulation during the AP response is mediated by cis-trans interactions between the hormone-responsive element (HRE) residing in the haptoglobin gene and inducible transcription factors STAT3 and C/EBP β. In male rats that have been subjected to chronic 50% dietary restriction (DR), the basal haptoglobin serum level is decreased. The aim of this study was to characterize the trans-acting factor(s) responsible for the reduction of haptoglobin expression in male rats subjected to 50% DR for 6 weeks. Protein-DNA interactions between C/EBP and STAT families of transcription factors and the HRE region of the haptoglobin gene were examined in livers of male rats subjected to DR, as well as during the AP response that was induced by turpentine administration. In DR rats, we observed associations between the HRE and C/EBPα/β, STAT5b and NF-κB p50, and the absence of interactions between STAT3 and NF-kB p65. Subsequent induction of the AP response in DR rats by turpentine administration elicited a normal, almost 2-fold increase in the serum haptoglobin level that was accompanied by HRE-binding of C/EBPβ, STAT3/5b and NF-kB p65/p50, and the establishment of interaction between STAT3 and NF-κB p65. These results suggest that STAT3 and NF-κB p65 crosstalk plays a central role while C/EBPβ acquires an accessory role in establishing the level of haptoglobin gene expression in male rats exposed to DR and AP stimuli.
authors.affiliation: Department of Molecular Biology, Institute for Biological Research, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia. auskokovic@ibiss.bg.ac.rs
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Uskoković
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dinić
authors.forename: Mirjana
authors.initials: M
authors.lastname: Mihailović
authors.forename: Nevena
authors.initials: N
authors.lastname: Grdović
authors.forename: Jelena
authors.initials: J
authors.lastname: Arambašić
authors.forename: Melita
authors.initials: M
authors.lastname: Vidaković
authors.forename: Desanka
authors.initials: D
authors.lastname: Bogojević
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ivanović-Matić
authors.forename: Vesna
authors.initials: V
authors.lastname: Martinović
authors.forename: Miodrag
authors.initials: M
authors.lastname: Petrović
authors.forename: Goran
authors.initials: G
authors.lastname: Poznanović
authors.forename: Ilijana
authors.initials: I
authors.lastname: Grigorov
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D031204:Caloric Restriction; D002846:Chromatography, Affinity; D006242:Haptoglobins / Q000378:metabolism*; D047468:Immunoprecipitation; D008297:Male; D051381:Rats; D020239:Receptor Cross-Talk / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D018709:Statistics, Nonparametric; D051996:Transcription Factor RelA / Q000378:metabolism*; D014425:Turpentine / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D006242:Haptoglobins; C498145:Rela protein, rat; D050796:STAT3 Transcription Factor; D051996:Transcription Factor RelA; D014425:Turpentine