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Journal of Histochemistry and Cytochemistry, Vol. 51, 297-302, March 2003, Copyright © 2003, The Histochemical Society, Inc.


ARTICLE

NAD(P)H:Quinone Oxidoreductase 1 Expression in Kidney Podocytes

Francesco Zappaa, Timothy Warda, Ennio Pedrinisb, John Butlera, and Alan McGowna
a CRC Department of Drug Development, Paterson Institute for Cancer Research and Christie Hospital NHS Trust, Manchester, United Kingdom
b Institute of Pathology of Southern Switzerland, Locarno, Switzerland

Correspondence to: Francesco Zappa, Dept. of Medical Oncology, Institute of Oncology of Southern Switzerland (IOSI), 6500 Bellinzona-TI, Switzerland. E-mail: fzappa@ticino.com

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a cytosolic two-electron reductase, and compounds of the quinone family such as mitomycin C are efficiently bioactivated by this enzyme. The observation that DT-diaphorase is highly expressed in many cancerous tissues compared to normal tissues has provided us with a potentially selective target that can be exploited in the design of novel anticancer agents. Because of the relative lack of information about the cell-specific expression of DT-diaphorase, the purpose of this study was to map the distribution of this enzyme in normal human tissues. Fifteen tissue samples from normal human kidney were analyzed for expression of DT-diaphorase by immunohistochemistry (two-step indirect method). We found a specific high expression of DT-diaphorase in glomerular visceral epithelial cells (podocytes). These results suggest that a high expression of DT-diaphorase in podocytes could play a major role in the pathogenesis of renal toxicity and mitomycin C-induced hemolytic uremic syndrome, in which injury to the glomerular filtration mechanism is the primary damage, leading to a cascade of deleterious events including microangiopathic hemolytic anemia and thrombocytopenia. This observation has potential therapeutic implications because the DT-diaphorase metabolic pathway is influenced by many agents, including drugs, diet, and environmental cell factors such as pH and oxygen tension.

(J Histochem Cytochem 51:297–302, 2003)

Key Words: DT-diaphorase, NQO1, kidney glomerulus drug effects, immunohistochemistry, P450-reductase


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