Renal CCAAT/enhancer-binding proteins in experimental diabetes mellitus

Ivan Z. Zador, Ching C. Hsieh, John Papaconstantinou

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

There is evidence that mediators of inflammation including components of the cytokine system are present in human and experimental diabetic kidney disease. CCAAT/enhancer-binding proteins (C/EBPs) represent a family of cytokine-inducible transcription factors. C/EBPs themselves regulate cytokine expression and also the expression of acute-phase reactants and connective tissue proteins. At least three C/EBP isoforms (α, β, δ) are known. Upon stimulation with cytokines or bacterial lipopolysaccharide, the expression of the α isoform typically decreases, and the expression of the β and/or δ isoforms increases. In view of the fact that components of the inflammatory response are present in diabetic kidney disease, there is a potential that the expression and activity of renal C/EBPs are altered in the diabetic state. In this study we sought to examine the status of C/EBP proteins in kidneys of rats with streptozotocin-induced diabetes mellitus. Diabetes was induced in 5 male Sprague-Dawley rats. Eight weight-matched non-diabetic rats were used as controls, Animals were sacrificed after 4 weeks, and the whole kidney nuclear protein was extracted. An electrophoretic mobility shift assay showed that DNA-binding activity was present in all five kidney nuclear extracts of the diabetic animals, but in only 2 out of 8 control samples (p < 0.05). A supershift assay showed that the DNA-bound protein complex consisted mainly of the C/EBPβ isoform. Western analysis showed an increase of the C/EBPβ protein in renal nuclear extracts of the diabetic animals compared to controls (p < 0.05). There was a decrease of the C/EBPα protein in the kidney nuclear extracts of the diabetic animals compared to controls (p < 0.05). We conclude that renal C/EBP dynamics are altered in experimental diabetes mellitus and that the patterns of C/EBP changes resemble those observed after cytokine or lipopolysaccharide stimulation.

Original languageEnglish (US)
Pages (from-to)312-316
Number of pages5
JournalNephron
Volume79
Issue number3
DOIs
StatePublished - 1998

Fingerprint

CCAAT-Enhancer-Binding Proteins
Experimental Diabetes Mellitus
Kidney
Cytokines
Protein Isoforms
Diabetic Nephropathies
Proteins
Lipopolysaccharides
Inflammation Mediators
Acute-Phase Proteins
DNA
Electrophoretic Mobility Shift Assay
Nuclear Proteins
Connective Tissue
Sprague Dawley Rats
Diabetes Mellitus
Transcription Factors

Keywords

  • CCAAT/enhancer-binding protein
  • Cytokine
  • Diabetes mellitus
  • Kidney, experimental diabetes

ASJC Scopus subject areas

  • Nephrology

Cite this

Renal CCAAT/enhancer-binding proteins in experimental diabetes mellitus. / Zador, Ivan Z.; Hsieh, Ching C.; Papaconstantinou, John.

In: Nephron, Vol. 79, No. 3, 1998, p. 312-316.

Research output: Contribution to journalArticle

Zador, Ivan Z. ; Hsieh, Ching C. ; Papaconstantinou, John. / Renal CCAAT/enhancer-binding proteins in experimental diabetes mellitus. In: Nephron. 1998 ; Vol. 79, No. 3. pp. 312-316.
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