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

N. Hill-Kapturczak, V. Thamilselvan, F. Liu, H. S. Nick, A. Agarwal

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

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 μM). 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-κB (NF-κB) with an IκBα 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-κB pathway.

Original languageEnglish (US)
Pages (from-to)F851-F859
JournalAmerican Journal of Physiology - Renal Physiology
Volume281
Issue number5 50-5
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Antioxidants
  • Nuclear factor-κB
  • Renal tubular injury

ASJC Scopus subject areas

  • Physiology
  • Urology

Fingerprint Dive into the research topics of 'Mechanism of heme oxygenase-1 gene induction by curcumin in human renal proximal tubule cells'. Together they form a unique fingerprint.

Cite this