TNFα-induced NF-κB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells

Alejandra G. Erlejman, Grayson Jaggers, Cesar G. Fraga, Patricia I. Oteiza

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Hexameric procyanidins inhibit TNFα-induced NF-κB activation in Caco-2 cells. Most of the physiological actions of high molecular weight procyanidins could be limited to the gut lumen. Transcription factor NF-κB plays a central role in inflammation including human intestinal bowel disease. We investigated the capacity of a hexameric procyanidin fraction (Hex) to prevent tumor necrosis factor alpha (TNFα)-induced NF-κB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5-20 μM) inhibited TNFα-induced NF-κB activation (IκB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-κB-DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-κB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and α-lipoic acid inhibited TNFα-induced oxidant increase but did not affect NF-κB activation. In summary, Hex can inhibit NF-κB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFα to its receptor and the subsequent NF-κB activation.

Original languageEnglish (US)
Pages (from-to)186-195
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume476
Issue number2
DOIs
StatePublished - Aug 15 2008

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Proanthocyanidins
Caco-2 Cells
Oxidants
Tumor Necrosis Factor-alpha
Chemical activation
B-Form DNA
Thioctic Acid
Intestinal Diseases
Acetylcysteine
Nitric Oxide Synthase Type II
Cell Communication
Phosphorylation
Transcription Factors
Molecular Weight
Cell membranes
Cell Membrane
Inflammation
Membranes
Molecular weight
Degradation

Keywords

  • Antioxidant
  • Cocoa
  • Flavanol
  • Flavonoid
  • Gastrointestinal tract
  • Inflammation
  • Intestinal barrier
  • Membrane interactions
  • Procyanidin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

TNFα-induced NF-κB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. / Erlejman, Alejandra G.; Jaggers, Grayson; Fraga, Cesar G.; Oteiza, Patricia I.

In: Archives of Biochemistry and Biophysics, Vol. 476, No. 2, 15.08.2008, p. 186-195.

Research output: Contribution to journalArticle

Erlejman, Alejandra G. ; Jaggers, Grayson ; Fraga, Cesar G. ; Oteiza, Patricia I. / TNFα-induced NF-κB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. In: Archives of Biochemistry and Biophysics. 2008 ; Vol. 476, No. 2. pp. 186-195.
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