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Disulfide S-monoxides convert xanthine dehydrogenase into oxidase in rat liver cytosol more potently than their respective disulfides.
Biol Pharm Bull. 2008 May; 31(5):1013-6.BP

Abstract

Xanthine oxidase (XO)/xanthine dehydrogenase (XD) oxidizes oxypurines to uric acid, with only the XO form producing reactive oxygen species. In the present study, the effects of cystamine S-monoxide and cystine S-monoxide (disulfide S-monoxides) on the conversion of XD to XO in rat liver were examined. A partially purified enzyme fraction from the rat liver was incubated with xanthine in the presence or absence of NAD+, and the uric acid formed was measured by HPLC. Under basal conditions, XO activity represented about 15% of the total XO plus XD activity. Cystamine S-monoxide and cystine S-monoxide converted XD into XO in a dose-dependent manner, and the concentrations required to increase XO activity by 50% were approximately 1 and 2 microM, respectively. Their respective thiols (cysteamine and cysteine) and disulfides (cystamine and cystine) up to 10 microM showed weak or no effects on the activities of XO and XD and their conversion. Experiments utilizing a sulfhydryl reducing reagent (dithiothreitol) and sulfhydryl modifiers (4,4'-dithiodipyridine and 1-fluoro-2,4-dinitrobenzene) indicated that disulfide S-monoxides-induced conversion of XD to XO occurs via disulfide bridge formation in XD, but not the modification of sulfhydryl groups. These results suggest that disulfide S-monoxides have the potential to increase the generation of reactive oxygen species through the conversion of XD to XO in liver.

Authors+Show Affiliations

Department of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. sakuma@gly.oups.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18451537

Citation

Sakuma, Satoru, et al. "Disulfide S-monoxides Convert Xanthine Dehydrogenase Into Oxidase in Rat Liver Cytosol More Potently Than Their Respective Disulfides." Biological & Pharmaceutical Bulletin, vol. 31, no. 5, 2008, pp. 1013-6.
Sakuma S, Fujita J, Nakanishi M, et al. Disulfide S-monoxides convert xanthine dehydrogenase into oxidase in rat liver cytosol more potently than their respective disulfides. Biol Pharm Bull. 2008;31(5):1013-6.
Sakuma, S., Fujita, J., Nakanishi, M., Wada, S. I., & Fujimoto, Y. (2008). Disulfide S-monoxides convert xanthine dehydrogenase into oxidase in rat liver cytosol more potently than their respective disulfides. Biological & Pharmaceutical Bulletin, 31(5), 1013-6.
Sakuma S, et al. Disulfide S-monoxides Convert Xanthine Dehydrogenase Into Oxidase in Rat Liver Cytosol More Potently Than Their Respective Disulfides. Biol Pharm Bull. 2008;31(5):1013-6. PubMed PMID: 18451537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disulfide S-monoxides convert xanthine dehydrogenase into oxidase in rat liver cytosol more potently than their respective disulfides. AU - Sakuma,Satoru, AU - Fujita,Junko, AU - Nakanishi,Masahiko, AU - Wada,Shun-ich, AU - Fujimoto,Yohko, PY - 2008/5/3/pubmed PY - 2008/6/20/medline PY - 2008/5/3/entrez SP - 1013 EP - 6 JF - Biological & pharmaceutical bulletin JO - Biol Pharm Bull VL - 31 IS - 5 N2 - Xanthine oxidase (XO)/xanthine dehydrogenase (XD) oxidizes oxypurines to uric acid, with only the XO form producing reactive oxygen species. In the present study, the effects of cystamine S-monoxide and cystine S-monoxide (disulfide S-monoxides) on the conversion of XD to XO in rat liver were examined. A partially purified enzyme fraction from the rat liver was incubated with xanthine in the presence or absence of NAD+, and the uric acid formed was measured by HPLC. Under basal conditions, XO activity represented about 15% of the total XO plus XD activity. Cystamine S-monoxide and cystine S-monoxide converted XD into XO in a dose-dependent manner, and the concentrations required to increase XO activity by 50% were approximately 1 and 2 microM, respectively. Their respective thiols (cysteamine and cysteine) and disulfides (cystamine and cystine) up to 10 microM showed weak or no effects on the activities of XO and XD and their conversion. Experiments utilizing a sulfhydryl reducing reagent (dithiothreitol) and sulfhydryl modifiers (4,4'-dithiodipyridine and 1-fluoro-2,4-dinitrobenzene) indicated that disulfide S-monoxides-induced conversion of XD to XO occurs via disulfide bridge formation in XD, but not the modification of sulfhydryl groups. These results suggest that disulfide S-monoxides have the potential to increase the generation of reactive oxygen species through the conversion of XD to XO in liver. SN - 0918-6158 UR - https://www.unboundmedicine.com/medline/citation/18451537/Disulfide_S_monoxides_convert_xanthine_dehydrogenase_into_oxidase_in_rat_liver_cytosol_more_potently_than_their_respective_disulfides_ L2 - http://joi.jlc.jst.go.jp/JST.JSTAGE/bpb/31.1013?from=PubMed DB - PRIME DP - Unbound Medicine ER -