NAD(P)H:Quinone Oxidoreductase 1 Expression in Kidney PodocytesFrancesco Zappaa, Timothy Warda, Ennio Pedrinisb, John Butlera, and Alan McGownaa 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 51:297302, 2003) Key Words: DT-diaphorase, NQO1, kidney glomerulus drug effects, immunohistochemistry, P450-reductase
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