DT-diaphorase is a ubiquitously expressed flavoenzyme responsible for the two-electron reduction of a number of quinone and other anticancer drugs. The majority of DT-diaphorase enzyme activity in human tissues is the product of the NQO1 gene. We have now identified a novel alternatively spliced form of human NQO1 mRNA lacking exon 4 at levels equal to or exceeding those of wild-type NQO1 mRNA....

The levels of NAD(P)H:(quinone-acceptor) oxidoreductase (EC.1.6.99.2) (DT-diaphorase) mRNA and enzyme activity have been studied in paired human normal lung and non-small cell lung tumor samples from patients with a history of cigarette smoking. There were significantly higher levels of DT-diaphorase mRNA (1.2 kilobases) in lung tumor compared to normal lung tissue of patients who had stopped s...

A newly discovered human diaphorase, designated diaphorase-4, which accounts for a major part of the diaphorase activity of most tissues but does not occur in erythrocytes, is described. In contrast with other human diaphorases, it is dependent on FAD for activity after electrophoresis, inhibited by low concentrations of dicoumarol and shows a marked affinity for Cibacron Blue. The molecular we...

We used the NADPH-diaphorase histochemical method as a potential marker for nitric oxide synthase (NOS)-containing nerve fibers innervating the pineal gland of the sheep. Nerve fibers containing NADPH-diaphorase activity provide dense innervation of the sheep pineal gland. The nerve fibers were located in the pineal capsule, in the connective tissue septae separating the lobull of the gland, an...

The experiments reported here were designed to test the hypothesis that the two-electron quinone reductase DT-diaphorase [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] functions to maintain membrane-bound coenzyme Q (CoQ) in its reduced antioxidant state, thereby providing protection from free radical damage. DT-diaphorase was isolated and purified from rat liver cytosol, and its abil...

reductase activity (MHR), measured by the Hegesh assay, decreases as normal red cells age. This probably accounts for the slighlty increased concentration of methemoglobin in older red cells. Exaggeration of normal MHR age lability was demonstrated in several individuals with various molecular abnormalities of NADH-diaphorase and was associated with more striking accumulation of methemoglobin i...

A histochemical method is described for the localization of triphosphopyridine nucleotide diaphorase using a recently synthesized tetrazolium salt (Nitro-BT). By virtue of the favorable histochemical properties of this reagent, it has been possible to demonstrate that whereas DPN diaphorase is usually restricted to the mitochondria, the TPN diaphorase activity of corresponding cells was distrib...

Quercetin is one of the most studied alimentary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its ortho-quinone/quinone methide, denoted as QQ. QQ is toxic since it is highly reactive towards thiols. DT-diaphorase (NQO1) might protect against QQ toxicity by reducing QQ to quercetin. However, conflicting data have been reported. The aim of the present study is to...

BACKGROUND To our knowledge, 17-allylamino,17-demethoxygeldanamycin (17AAG) is the first inhibitor of heat shock protein 90 (Hsp90) to enter a phase I clinical trial in cancer. Inhibition of Hsp90, a chaperone protein (a protein that helps other proteins avoid misfolding pathways that produce inactive or aggregated states), leads to depletion of important oncogenic proteins, including Raf-1 and...