Diabetes-induced activation of canonical and noncanonical nuclear factor-κB pathways in renal cortex

Jonathan Starkey, Sigmund J. Haidacher, Wanda S. LeJeune, Xiaoquan Zhang, Brian C. Tieu, Sanjeev Choudhary, Allan R. Brasier, Larry Denner, Ronald Tilton

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Evidence of diabetes-induced nuclear factor-κB (NF-κB) activation has been provided with DNA binding assays or nuclear localization with immunohistochemistry, but few studies have explored mechanisms involved. We examined effects of diabetes on proteins comprising NF-κB canonical and noncanonical activation pathways in the renal cortex of diabetic mice. Plasma concentrations of NF-κB-regulated cytokines were increased after 1 month of hyperglycemia, but most returned to control levels or lower by 3 months, when the same cytokines were increased significantly in renal cortex. Cytosolic content of NF-κB canonical pathway proteins did not differ between experimental groups after 3 months of diabetes, while NF-κB noncanonical pathway proteins were affected, including increased phosphorylation of inhibitor of κB kinase-α and several fold increases in NF-κB-inducing kinase and RelB, which were predominantly located in tubular epithelial cells. Nuclear content of all NF-κB pathway proteins was decreased by diabetes, with the largest change in RelB and p50 (approximately twofold decrease). Despite this decrease, measurable increases in protein binding to DNA in diabetic versus control nuclear extracts were observed with electrophoretic mobility shift assay. These results provide evidence for chronic NF-κB activation in the renal cortex of db/db mice and suggest a novel, diabetes-linked mechanism involving both canonical and noncanonical NF-κB pathway proteins.

Original languageEnglish (US)
Pages (from-to)1252-1259
Number of pages8
JournalDiabetes
Volume55
Issue number5
DOIs
StatePublished - 2006

Fingerprint

Kidney
Proteins
Phosphotransferases
Cytokines
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Nuclear Proteins
Hyperglycemia
Epithelial Cells
Immunohistochemistry
Phosphorylation
DNA

Keywords

  • DTT, dithiothreitol
  • EMSA, electrophoretic mobility shift assay
  • IκB, inhibitor of κB
  • IKK, inhibitor of κB kinase
  • IL, interleukin
  • NF-κB, nuclear factor-κB
  • NIK, NF-κB-inducing kinase
  • TNF, tumor necrosis factor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Starkey, J., Haidacher, S. J., LeJeune, W. S., Zhang, X., Tieu, B. C., Choudhary, S., ... Tilton, R. (2006). Diabetes-induced activation of canonical and noncanonical nuclear factor-κB pathways in renal cortex. Diabetes, 55(5), 1252-1259. https://doi.org/10.2337/db05-1554

Diabetes-induced activation of canonical and noncanonical nuclear factor-κB pathways in renal cortex. / Starkey, Jonathan; Haidacher, Sigmund J.; LeJeune, Wanda S.; Zhang, Xiaoquan; Tieu, Brian C.; Choudhary, Sanjeev; Brasier, Allan R.; Denner, Larry; Tilton, Ronald.

In: Diabetes, Vol. 55, No. 5, 2006, p. 1252-1259.

Research output: Contribution to journalArticle

Starkey, J, Haidacher, SJ, LeJeune, WS, Zhang, X, Tieu, BC, Choudhary, S, Brasier, AR, Denner, L & Tilton, R 2006, 'Diabetes-induced activation of canonical and noncanonical nuclear factor-κB pathways in renal cortex', Diabetes, vol. 55, no. 5, pp. 1252-1259. https://doi.org/10.2337/db05-1554
Starkey, Jonathan ; Haidacher, Sigmund J. ; LeJeune, Wanda S. ; Zhang, Xiaoquan ; Tieu, Brian C. ; Choudhary, Sanjeev ; Brasier, Allan R. ; Denner, Larry ; Tilton, Ronald. / Diabetes-induced activation of canonical and noncanonical nuclear factor-κB pathways in renal cortex. In: Diabetes. 2006 ; Vol. 55, No. 5. pp. 1252-1259.
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