title: Possible mechanism of superoxide formation through redox cycling of plumbagin in pig heart.
abstract: The purpose of this study is to elucidate the possible mechanism of superoxide formation through redox cycling of plumbagin (PLG) in pig heart. Of four 1,4-naphthoquinones tested in this study, PLG was most efficiently reduced in the cytosolic fraction of pig heart. On the other hand, lawsone (LAS) was little reduced. Thus, whether or not PLG and LAS induce the formation of superoxide anion radical in pig heart cytosol was examined, by using the methods of cytochrome c reduction and chemiluminescence. PLG significantly induced the formation of superoxide anion radical, even though LAS had no ability to mediate superoxide formation. PLG was a significant inhibitor for the stereoselective reduction of 4-benzoylpyridine (4-BP) catalyzed by tetrameric carbonyl reductase (TCBR) in pig heart cytosol. Furthermore, PLG was confirmed to competitively inhibit the 4-BP reduction, and the optimal pH for the PLG reduction was around 6.0 similar to that for the 4-BP reduction. These results suggest that PLG mediates superoxide formation through its redox cycling involved in the two-electron reduction catalyzed by TCBR, and induces oxidative stress in pig heart.
authors.affiliation: Faculty of Education, Kumamoto University, 2-40-1 Kurokami, Kumamoto 860-8555, Japan. hshimada@gpo.kumamoto-u.ac.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Reiko
authors.initials: R
authors.lastname: Morita
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mizuno
authors.forename: Kousei
authors.initials: K
authors.lastname: Gotoh
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Higuchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Yorishige
authors.initials: Y
authors.lastname: Imamura
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013552:Swine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D011725:Pyridines; D013481:Superoxides; C066738:4-benzoylpyridine; D045304:Cytochromes c; C014758:plumbagin