+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase



Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase



Toxicology and Applied Pharmacology 359: 102-107



NADH cytochrome b5 reductase mediates electron transfer from NADH to cytochrome b5 utilizing flavin adenine dinucleotide as a redox cofactor. Reduced cytochrome b5 is an important cofactor in many metabolic reactions including cytochrome P450-mediated xenobiotic metabolism, steroid biosynthesis and fatty acid metabolism, hemoglobin reduction, and methionine and plasmalogen synthesis. Using recombinant human enzyme, we discovered that cytochrome b5 reductase mediates redox cycling of a variety of quinones generating superoxide anion, hydrogen peroxide, and, in the presence of transition metals, hydroxyl radicals. Redox cycling activity was oxygen-dependent and preferentially utilized NADH as a co-substrate; NADH was 5-10 times more active than NADPH in supporting redox cycling. Redox cycling activity was greatest for 9,10-phenanthrenequinone and 1,2-naphthoquinone, followed by 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone (menadione), nitrofurantoin and 2-hydroxyestradiol. Using menadione as the substrate, quinone redox cycling was found to inhibit reduction of cytochrome b5 by cytochrome b5 reductase, as measured by heme spectral changes in cytochrome b5. Under anaerobic conditions where redox cycling is inhibited, menadione had no effect on the reduction of cytochrome b5. Chemical redox cycling by cytochrome b5 reductase may be important in generating cytotoxic reactive oxygen species in target tissues. This activity, together with the inhibition of cytochrome b5 reduction by redox-active chemicals and consequent deficiencies in available cellular cytochrome b5, are likely to contribute to tissue injury following exposure to quinones and related redox active chemicals.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 065896085

Download citation: RISBibTeXText

PMID: 30222979

DOI: 10.1016/j.taap.2018.09.011


Related references

Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radical Biology and Medicine 44(6): 1169-1179, 2008

Aldo-keto reductase 1C15 as a quinone reductase in rat endothelial cell: its involvement in redox cycling of 9,10-phenanthrenequinone. Free Radical Research 45(7): 848-857, 2011

Protection against reactive oxygen species by NAD(P)H: quinone reductase induced by the dietary antioxidant butylated hydroxyanisole (BHA). Decreased hepatic low-level chemiluminescence during quinone redox cycling. Febs Letters 169(1): 63-66, 1984

Redox cycling of bleomycin-Fe(III) and DNA degradation by isolated NADH-cytochrome b5 reductase: involvement of cytochrome b5. Molecular Pharmacology 34(4): 578-583, 1988

Redox cycling of the bleomycin iron complex by isolated microsomal nadh cytochrome b 5 reductase and cytochrome b 5. Naunyn-Schmiedeberg's Archives of Pharmacology 337(SUPPL): R21, 1988

Detoxification by quinone reductase of reactive intermediates generated during redox cycling of estrogen. Proceedings of the American Association for Cancer Research Annual Meeting 28: 123, 1987

In cellulo monitoring of quinone reductase activity and reactive oxygen species production during the redox cycling of 1,2 and 1,4 quinones. Free Radical Biology and Medicine 89: 126-134, 2016

Redox cycling of Fe(III)-bleomycin by NADPH-cytochrome P-450 reductase. Biochemical Pharmacology 30(24): 3385-3388, 1981

Role of glutathione and nadph quinone oxido reductase dt diaphorase in determining low level chemi luminescence during redox cycling of menadione. Bors, W , M Saran And D Tait (Ed ) Oxygen Radicals in Chemistry And Biology; Proceedings Of The 3rd International Conference, Neuherberg, West Germany, July 10-15, 1983 Xix+1029p Walter De Gruyter: Berlin, West Germany; New York, N Y , Usa Illus P331-334, 1984

Structure and biogenesis of succinate ubi quinone reductase and ubi quinone cytochrome c reductase in neurospora crassa mitochondria. Lee, C P , G Schatz And L Ernster (Ed ) Membrane Bioenergetics; Based on The International Workshop; Bloomfield Hills, Mich , Usa, July 5-7, 1979 Xxxiv+609p Addison-Wesley Publishing Co , Inc : Reading, Mass , Usa Illus Paper P119-132, 1979, 1980

Distinct roles of cytochrome P450 reductase in mitomycin C redox cycling and cytotoxicity. Molecular Cancer Therapeutics 9(6): 1852-1863, 2010

Redox cycling of resorufin catalyzed by rat liver microsomal NADPH-cytochrome P450 reductase. Archives of Biochemistry and Biophysics 268(2): 605-616, 1989

Oxy radical formation during redox cycling of the bleomycin-iron (III) complex by NADPH-cytochrome P-450 reductase. Biochemical Pharmacology 34(17): 3091-3094, 1985

Temporary decrease in renal quinone reductase activity induced by chronic administration of estradiol to male Syrian hamsters. Increased superoxide formation by redox cycling of estrogen. Journal of Biological Chemistry 263(8): 3646-3651, 1988

Liver nuclear NADPH-cytochrome P-450 reductase may be involved in redox cycling of bleomycin-Fe(III), oxy radical formation and DNA damage. Free Radical Research Communications 2(4-6): 271-277, 1987