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Articles in PresS, published online ahead of print August 9, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.0140.2001
Submitted on May 8, 2001
Accepted on June 27, 2001
1 Medicine, University of Florida, Gainesville, Fl, USA
* To whom correspondence should be addressed. E-mail: agarwal{at}nersp.nerdc.ufl.edu.
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 activation of the HO-1 gene. To elucidate the molecular mechanism of HO-1 induction we examined the effects of 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 which was associated with increased HO-1 protein. Co-incubation of curcumin with actinomycin D completely blocked the upregulation of HO-1 mRNA. Blockade of NF-
B, with an IB
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-B pathway.
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