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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3494

Title: Hidden Antioxidative Functions of Reduced Nicotinamide Adenine Dinucleotide Coexisting with Hemoglobin.
Other Titles: ヘモグロビンと共存する還元型ニコチンアミドアデニンジヌクレオチドの隠れた抗酸化機能
Authors: Yamada, Magohei
Sakai, Hiromi
Issue Date: 21-Jul-2017
Publisher: American Chemical Society
Citation: ACS chemical biology Vol.12 No.7 p.1820-1829 (2017 Jul)
Abstract: Ferrous oxyhemoglobin (HbO2) in red blood cells (RBCs) invariably and slowly autoxidizes to form ferric methemoglobin (metHb). However, the level of metHb is always maintained below 0.5% by intracellular metHb reduction of enzymatic systems with coenzymes, such as reduced nicotinamide adenine dinucleotide (NADH), and by superoxide dismutase (SOD) and catalase (CAT), which eliminate reactive oxygen species. Unquestionably, NADH cannot reduce metHb without the corresponding enzymatic system. Our study, however, demonstrated that a high concentration of NADH (100-fold of normal level, equimolar to HbO2) retarded autoxidation of HbO2 in a highly purified Hb solution with no enzymatic system. Furthermore, an inhibitory effect of NADH on metHb formation was observed with additions of oxidants such as H2O2, NO, and NaNO2. Our mechanism assessment elucidated extremely high pseudo-CAT and pseudo-SOD activities of NADH with coexistence of HbO2, and reactivity of NADH with NO. We prepared a model of RBCs (Hb-vesicles, Hb-V) encapsulating purified HbO2 solution and NADH, but no enzymatic system within liposome. We confirmed the inhibitory effect of NADH on both autoxidation and oxidant-induced metHb formation. In addition, an intravenous administration of these Hb-Vs to rats caused significant retardation of metHb formation by approximately 50% compared to the case without NADH coencapsulation. Based on these results, we elucidated a new role of NADH, that is, antioxidative effect via interaction with Hb, in addition to its classical role as a coenzyme.
Description: 博士(医学)・甲第687号・平成30年9月26日
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS chemical biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/ 10.1021/acschembio.7b00174
URI: http://hdl.handle.net/10564/3494
ISSN: 15548929
Academic Degrees and number: 24601A687
Degree-granting date: 2018-09-26
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2018年度

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