NAD + deficiency plays essential roles in the hyperuricemia of stroke-prone spontaneously hypertensive rat via xanthine dehydrogenase to xanthine oxidase conversion.

Autor: Ferdaus SA; Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan., Ohara H; Department of Functional Pathology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan., Matsuo H; Institute of Experimental Animals, Interdisciplinary Center for Science Research, Head Office for research and academic Information, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan., Kawakami K; Institute of Experimental Animals, Interdisciplinary Center for Science Research, Head Office for research and academic Information, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan., Takeuchi F; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo, 162-8655, Japan., Fujikawa K; Department of Functional Pathology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan., Kawakita E; Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan., Kato N; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo, 162-8655, Japan., Nabika T; Department of Functional Pathology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan., Kanasaki K; Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan; The Center for Integrated Kidney Research and Advance, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, 693-8501, Japan. Electronic address: kkanasak@med.shimane-u.ac.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 12; Vol. 744, pp. 151136. Date of Electronic Publication: 2024 Dec 12.
DOI: 10.1016/j.bbrc.2024.151136
Abstrakt: Inhibition of xanthine oxidoreductase (XOR) was shown to ameliorate the stroke susceptibility in the stroke-prone spontaneously hypertensive rat (SHRSP), suggesting hyperuricemia had a pathological role in this rat model. In this study, we thus aimed to explore mechanisms inducing hyperuricemia in SHRSP. XOR is known to have two forms, xanthine dehydrogenase (XDH) as the prototype and xanthine oxidase (XO) as the converted form through cleavage of a peptide bond or through formation of disulfide bonds in the enzyme. XO was shown to have a greater activity to produce UA and oxidative stress. We thus hypothesized that the excess conversion to XO caused the higher UA level in SHRSP. Male SHRSP at 10 weeks of age showed a higher serum level of UA and a higher activity of XO than those in Wistar-Kyoto rat. As the protein level of the total XOR did not differ between the two strains, the conversion to XO seemed responsible for the high UA level in SHRSP. Meanwhile, NAD + level in SHRSP was lower than that in WKY, suggesting that low NAD + promoted the conversion to XO in this strain. ß-nicotinamide mononucleotide (NMN) supplementation for 2 weeks increased NAD + level and reduced the serum UA level as well as the XO activity in SHRSP. These observations supported that a low NAD + accelerated the conversion of XDH to XO in SHRSP, which resulted in high UA. The current study suggested the potential significance of NMN supplementation in the treatment of hyperuricemia in humans.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:K.K. Lecture Fees: Boehringer Ingelheim Japan, Eli Lilly Japan, Astellas, Novo Nordisk Pharma, Mitsubishi Tanabe, Daiichi Sankyo, Sanofi, Sumitomo Pharma, Kowa, Kyowa Kirin, Taisho, AstraZeneca, Bayer, Novartis, OtsukaCollaboration: Boehringer Ingelheim Japan, Boehringer-Ingelheim (Germany), Kowa, Mitsubishi Tanabe, BayerResearch support: Boehringer Ingelheim Japan, Nipro, Life ScanAcknowledgement: The author would represent cordial thanks to Abe Yoando Pharma, CO. Ltd for generously providing NMN.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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