2.50
Hdl Handle:
http://hdl.handle.net/10541/82353
Title:
NAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes.
Authors:
Zappa, Francesco; Ward, Timothy H; Pedrinis, Ennio; Butler, John; McGown, Alan T
Abstract:
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.
Affiliation:
CRC Department of Drug Development, Paterson Institute for Cancer Research and Christie Hospital NHS Trust, Manchester, United Kingdom. fzappa@ticino.com
Citation:
NAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes. 2003, 51 (3):297-302 J. Histochem. Cytochem.
Journal:
The Journal of Histochemistry and Cytochemistry
Issue Date:
Mar-2003
URI:
http://hdl.handle.net/10541/82353
PubMed ID:
12588957
Type:
Article
Language:
en
ISSN:
0022-1554
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorZappa, Francesco-
dc.contributor.authorWard, Timothy H-
dc.contributor.authorPedrinis, Ennio-
dc.contributor.authorButler, John-
dc.contributor.authorMcGown, Alan T-
dc.date.accessioned2009-09-23T13:18:09Z-
dc.date.available2009-09-23T13:18:09Z-
dc.date.issued2003-03-
dc.identifier.citationNAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes. 2003, 51 (3):297-302 J. Histochem. Cytochem.en
dc.identifier.issn0022-1554-
dc.identifier.pmid12588957-
dc.identifier.urihttp://hdl.handle.net/10541/82353-
dc.description.abstractNAD(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.en
dc.language.isoenen
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshKidney-
dc.subject.meshKidney Glomerulus-
dc.subject.meshNAD(P)H Dehydrogenase (Quinone)-
dc.subject.meshUrothelium-
dc.titleNAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Drug Development, Paterson Institute for Cancer Research and Christie Hospital NHS Trust, Manchester, United Kingdom. fzappa@ticino.comen
dc.identifier.journalThe Journal of Histochemistry and Cytochemistryen

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