Nrf2 regulates the alternative first exons of CD36 in macrophages through specific antioxidant response elements

Atsushi Maruyama, Saho Tsukamoto, Keizo Nishikawa, Aruto Yoshida, Nobuhiko Harada, Kiyoto Motojima, Tetsuro Ishii, Akio Nakane, Masayuki Yamamoto, Ken Itoh

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


We previously demonstrated that Nrf2 regulates oxidized LDL-mediated CD36 expression in macrophages. The current study aimed to determine the mechanism of Nrf2-mediated macrophage CD36 induction. Treatment with the Nrf2 activator diethylmaleate, but not PPARγ specific ligands, caused marked upregulation of CD36 in mouse macrophage RAW264.7 cells. Similarly, Nrf2 activators induced CD36 expression in bone marrow-derived macrophages in a Nrf2-dependent manner. Induced expression of the three alternative first exons of mouse CD36, deemed 1A, 1B, and 1C, occurred upon Nrf2 activation with exon1A mainly contributing to the CD36 expression. Four antioxidant response elements (AREs) lie within close proximity to these three exons, and chromatin immunoprecipitation assays demonstrated that two AREs upstream of exon1A, the distal 1A-ARE1, and the proximal 1A-ARE2, were Nrf2-responsive. Luciferase reporter assays conclusively demonstrated that 1A-ARE2 is the critical regulatory element for the Nrf2-mediated gene expression. Thus Nrf2 directly regulates CD36 gene expression by binding to 1A-ARE2.

Original languageEnglish
Pages (from-to)139-145
Number of pages7
JournalArchives of Biochemistry and Biophysics
Issue number1
Publication statusPublished - 2008 Sep 1


  • 15-deoxy-Δ-prostaglandin J
  • Alternative first exons
  • Antioxidant response element (ARE)
  • Macrophage
  • Mouse CD36
  • Nrf2
  • Scavenger receptors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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