[30] DT-diaphorase: Purification, properties, and function

Lind, Christina; Cadenas, Enrique; Hochstein, Paul; Ernster, Lars

doi:10.1016/0076-6879(90)86122-c

Cited by 286 publications

(182 citation statements)

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“…radical semiquinones, but form relatively stable hydroquinones that, depending on the functional groups present, can be further stabilized by conjugation (Cadenas et al, 1992;Testa, 1995). Two electron transfers protect the cell against reactive oxygen intermediates generated by univalent reducing enzymes (Lind et al, 1990;Ross et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

et al. 2010

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Parasitic plants in the Orobanchaceae develop haustoria in response to contact with host roots or chemical haustoriainducing factors. Experiments in this manuscript test the hypothesis that quinolic-inducing factors activate haustorium development via a signal mechanism initiated by redox cycling between quinone and hydroquinone states. Two cDNAs were previously isolated from roots of the parasitic plant Triphysaria versicolor that encode distinct quinone oxidoreductases. QR1 encodes a single-electron reducing NADPH quinone oxidoreductase similar to z-crystallin. The QR2 enzyme catalyzes two electron reductions typical of xenobiotic detoxification. QR1 and QR2 transcripts are upregulated in a primary response to chemical-inducing factors, but only QR1 was upregulated in response to host roots. RNA interference technology was used to reduce QR1 and QR2 transcripts in Triphysaria roots that were evaluated for their ability to form haustoria. There was a significant decrease in haustorium development in roots silenced for QR1 but not in roots silenced for QR2. The infrequent QR1 transgenic roots that did develop haustoria had levels of QR1 similar to those of nontransgenic roots. These experiments implicate QR1 as one of the earliest genes on the haustorium signal transduction pathway, encoding a quinone oxidoreductase necessary for the redox bioactivation of haustorial inducing factors.

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Section: Discussionmentioning

confidence: 99%

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

et al. 2010

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“…NQO1 activity was measured as described in ref. 33 by following the decrease in NADH absorbance at 340 nm by using Sunrise remote control spectrophotometer (Tecan). The reaction mixture in a final volume of 200 l contained 25 mM Tris⅐HCl (pH 7.5), 0.01% Tween 20, 0.7 mg͞ml BSA (pH 7.4), 40 M menadione, 5 M FAD, 200 M NADH, and 50 ng of recombinant NQO1 or cell extract.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of NAD(P)H:quinone oxidoreductase 1 activity and induction of p53 degradation by the natural phenolic compound curcumin

Tsvetkov

Asher

Reiss

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

140

111

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NAD(P)H:quinone oxidoreductase 1 (NQO1) regulates the stability of the tumor suppressor WT p53. NQO1 binds and stabilizes WT p53, whereas NQO1 inhibitors including dicoumarol and various other coumarins and flavones induce ubiquitin-independent proteasomal p53 degradation and thus inhibit p53-induced apoptosis. Here, we show that curcumin, a natural phenolic compound found in the spice turmeric, induced ubiquitin-independent degradation of WT p53 and inhibited p53-induced apoptosis in normal thymocytes and myeloid leukemic cells. Like dicoumarol, curcumin inhibited the activity of recombinant NQO1 in vitro, inhibited the activity of endogenous cellular NQO1 in vivo, and dissociated NQO1-WT p53 complexes. Neither dicoumarol nor curcumin dissociated the complexes of NQO1 and the human cancer hot-spot p53 R273H mutant and therefore did not induce degradation of this mutant. NQO1 knockdown by small-interfering RNA induced degradation of both WT p53 and the p53 R273H mutant. The results indicate that curcumin induces p53 degradation and inhibits p53-induced apoptosis by an NQO1-dependent pathway.NQO1-dependent pathway ͉ disruption of NQO1-p53 binding ͉ cancer hot-spot p53 mutant ͉ p53-induced apoptosis W ild-type p53 is a labile tumor suppressor protein whose cellular level is mainly regulated by its rate of proteasomal degradation (reviewed in ref. 1). WT p53 protein can induce growth arrest (1-4) or apoptosis (5-8) and can thus prevent accumulation of DNA-damaged cells that could lead to the development of cancer (reviewed in refs. 1, 9, and 10). This tumor-suppressing activity of WT p53 is abolished by mutations in the p53 gene that occur in Ͼ50% of human cancers (1,11,12), and the mutant proteins often accumulate in the cancer cells (13). Degradation of p53 is mediated by two alternative pathways, ubiquitin-independent (14, 15) or ubiquitin-dependent. Ubiquitin-dependent degradation of p53 is mediated by different ubiquitin E3 ligases, including Mdm2 (16,17), Pirh2 (18), and Cop1 (19), that bind and ubiquitinate p53, targeting it to degradation via the 26S proteasome. The ubiquitin-independent pathway is regulated by NAD(P)H:quinone oxidoreductase 1 (NQO1) (14,15,20,21) and is mediated via the 20S proteasome (22). We have shown that NQO1 stabilizes p53, so that NQO1 overexpression increases p53 levels (20, 21), whereas NQO1 knockdown by small interfering RNA (siRNA) decreases the level of p53 (14). NQO1 binds to p53 (23, 24) and dicoumarol, an inhibitor of NQO1 activity that competes with NAD(P)H for binding to NQO1, disrupts NQO1-p53 binding (23), and induces ubiquitin-independent proteasomal degradation of p53 (14,15,20,21,23). Various other coumarins and flavones that also compete with NAD(P)H for binding to NQO1 also induce ubiquitin-independent p53 degradation (23). However, unlike WT p53 and some p53 mutants, the most frequent hot-spot human cancer p53 mutants (11, 12) were resistant to dicoumarolinduced degradation by increased binding to NQO1 (23).Curcumin, a natural phenolic compound found in the spice ...

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“…The NQO1 acts as superoxide scavenger, and it prevents the generation of ROS such as superoxide and hydrogen peroxide. 37,38 HMOX1 is an essential enzyme in heme catabolism and is induced by oxidative stress. Both in vitro and in vivo studies have reported that HMOX1 is susceptible to oxidative stress.…”

Section: Journal Of Clinical and Experimental Hepatologymentioning

confidence: 99%

Silibinin Inhibits Proliferation and Migration of Human Hepatic Stellate LX-2 Cells

Ezhilarasan

Evraerts

Sid

et al. 2016

Journal of Clinical and Experimental Hepatology

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Background: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line. Methods: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 mM). After 24 and 96 h of treatment, total cell number was determined by counting. Cytotoxicity was evaluated by trypan blue dye exclusion test. The expression profile of cMyc and peroxisome proliferator-activated receptor-g (PPAR-g) protein expressions was evaluated by Western blotting. Oxidative stress marker genes profile was quantified using qPCR. The migratory response of HSCs was observed by scrape wound healing assay. Results: SBN treatments significantly inhibit the LX-2 cell proliferation (without affecting its viability) in dose dependent manner. This treatment also retards the migration of LX-2 cells toward injured area. In Western blotting studies SBN treatment up regulated the protein expressions of PPAR-g and inhibited cMyc. Conclusion: The present study shows that SBN retards the proliferation, activation and migration of LX-2 cells without inducing cytotoxicity and oxidative stress. The profound effects could be due to cell cycle arresting potential of SBN. ( J CLIN EXP HEPATOL 2016;6:167-174)

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[30] DT-diaphorase: Purification, properties, and function

Cited by 286 publications

References 54 publications

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

Inhibition of NAD(P)H:quinone oxidoreductase 1 activity and induction of p53 degradation by the natural phenolic compound curcumin

Silibinin Inhibits Proliferation and Migration of Human Hepatic Stellate LX-2 Cells

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