NAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes.
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.
Zappa
Francesco
F
CRC Department of Drug Development, Paterson Institute for Cancer Research and Christie Hospital NHS Trust, Manchester, United Kingdom. fzappa@ticino.com
Ward
Timothy
T
Pedrinis
Ennio
E
Butler
John
J
McGown
Alan
A
D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000166:cytology / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D019459:Urothelium / Q000166:cytology / Q000201:enzymology
D016660:NAD(P)H Dehydrogenase (Quinone)