Effect of TNFα on activities of different promoters of human apolipoprotein A-I gene

Sergey V. Orlov, Denis A. Mogilenko, Vladimir S. Shavva, Ella B. Dizhe, Irina A. Ignatovich, Andrej P. Perevozchikov

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19 Scopus citations


Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1β and TNFα. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNFα-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNFα on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNFα leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNFα. The MEK1/2-ERK1/2 cascade and nuclear receptors PPARα and LXRs are important for TNFα-mediated apoA-I promoter switching.

Original languageEnglish
Pages (from-to)224-230
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Jul 2010


  • Alternative transcription
  • Apolipoprotein A-I
  • HDLs
  • LXR
  • MEK1/2
  • PPARα
  • TNFα


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