Mechanism of heme oxygenase-1 gene induction by curcumin in human renal proximal tubule cells.

Academic Article


  • Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation, releasing iron, carbon monoxide, and biliverdin. Induction of HO-1 occurs as an adaptive and protective response to several inflammatory stimuli. The transcription factor activator protein-1 (AP-1) has been implicated in the activation of the HO-1 gene. To elucidate the molecular mechanism of HO-1 induction, we examined the effects of diferuloylmethane (curcumin), an inhibitor of the transcription factor AP-1. Surprisingly, curcumin by itself was a very potent inducer of HO-1. Curcumin has anti-inflammatory, antioxidant, and renoprotective effects. To evaluate the mechanism of curcumin-mediated induction of HO-1, confluent human renal proximal tubule cells were exposed to curcumin (1-8 microM). We observed a time- and dose-dependent induction of HO-1 mRNA that was associated with increased HO-1 protein. Coincubation of curcumin with actinomycin D completely blocked the upregulation of HO-1 mRNA. Blockade of nuclear factor-kappaB (NF-kappaB) with an IkappaBalpha phosphorylation inhibitor attenuated curcumin-mediated induction of HO-1 mRNA and protein. These data demonstrate that curcumin induces HO-1 mRNA and protein in renal proximal tubule cells. HO-1 induction by curcumin is mediated, at least in part, via transcriptional mechanisms and involves the NF-kappaB pathway.
  • Keywords

  • Antioxidants, Cells, Cultured, Curcumin, Dactinomycin, Drug Stability, Enzyme Inhibitors, Ferritins, Gene Expression, Half-Life, Heme Oxygenase (Decyclizing), Heme Oxygenase-1, Humans, Immunoblotting, Kidney Tubules, Proximal, Membrane Proteins, NF-kappa B, Protein-Tyrosine Kinases, RNA, Messenger, Transcription Factor AP-1
  • Digital Object Identifier (doi)

    Author List

  • Hill-Kapturczak N; Thamilselvan V; Liu F; Nick HS; Agarwal A
  • Start Page

  • F851
  • End Page

  • F859
  • Volume

  • 281
  • Issue

  • 5