Jurkat Cells Respond to Biotin Deficiency With Increased Nuclear Translocation of NF-kappaB, Mediating Cell Survival

Int J Vitam Nutr Res. 2004 May;74(3):209-16. doi: 10.1024/0300-9831.74.3.209.

Abstract

Members of the NF-kappaB family of transcription factors cause transcriptional activation of anti-apoptotic genes. Here we determined whether survival of biotin-deficient cells is mediated by nuclear translocation of NF-kappaB. Human T (Jurkat) cells were cultured in biotin-deficient or biotin-supplemented media; nuclear translocation of NF-kappaB was stimulated with phytohemagglutinin and phorbol-12-myristate-13-acetate. Nuclear abundance of two members (p50 and p65) of the NF-kappaB family was greater in biotin-deficient compared to biotin-supplemented cells; this effect was mediated by phosphorylation of IkappaBalpha. The nuclear enrichment of p50 and p65 in biotin-deficient cells was associated with transcriptional activation of NF-kappaB-depedent genes such as the tumor suppressor gene p53 and the anti-apoptotic gene Bfl-1/A1. Biotin-deficient cells exhibited smaller activities of the apoptotic enzyme caspase-3 in response to treatment with tumor necrosis factor alpha, and decreased cell death in response to serum starvation compared to biotin-supplemented cells. These findings suggest that NF-kappaB mediates survival of biotin-deficient cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / genetics
  • Biological Transport
  • Biotin / administration & dosage
  • Biotin / deficiency*
  • Caspase 3
  • Caspases / metabolism
  • Cell Nucleus / metabolism*
  • Cell Survival*
  • Gene Expression Regulation
  • Genes, p53 / genetics
  • Humans
  • I-kappa B Proteins / metabolism
  • Jurkat Cells
  • Minor Histocompatibility Antigens
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Phytohemagglutinins / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • BCL2-related protein A1
  • I-kappa B Proteins
  • Minor Histocompatibility Antigens
  • NF-kappa B
  • NFKBIA protein, human
  • Phytohemagglutinins
  • Proto-Oncogene Proteins c-bcl-2
  • NF-KappaB Inhibitor alpha
  • Biotin
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Tetradecanoylphorbol Acetate