フジサワ　アキオ   藤沢　章雄    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2022/09
形態種別	学術論文
標題	Reduced prosaposin levels in HepG2 cells with long-term coenzyme Q10 deficiency
執筆形態	共著
掲載誌名	Journal of Clinical Biochemistry and Nutrition
掲載区分	国外
出版社・発行元	Society for Free Radical Research Japan
巻・号・頁	71(2),pp.97-102
総ページ数	6
著者・共著者	Takeuchi H, Sugawara K, Okamoto M, Nakamura A, Tanaka T, Fujita Y, Ishiguro K, Yamazaki H, Okada M, Mikami A, Fujisawa A, Yamamoto Y, Kashiba M.
概要	Glycosphingolipids are involved in intercellular signaling, adhe-sion, proliferation, and differentiation. Saposins A, B, C, and D are cofactors required for glycosphingolipid hydrolysis. Saposins A-D are present in series in a common precursor protein, prosaposin. Thus, glycosphingolipids amounts depend on prosaposin cellular levels. We previously reported that prosaposin and saposin B bind coenzyme Q10 in human cells. Coenzyme Q10 is an essential lipid of the mitochondrial electron transport system, and its reduced form is an important antioxidant. Coenzyme Q10 level decrease in aging and in various progressive diseases. Therefore, it is interesting to understand the cellular response to long-term coenzyme Q10 deficiency. We established a long-term coenzyme Q10 deficient cell model by using the coenzyme Q10 biosynthesis inhibitor, 4-nitrobenzoate. The levels of coenzyme Q10 were reduced by 4-nitrobenzoate in HepG2 cells. Administration of 4-nitrobenzoate also decreased prosaposin protein and mRNA levels. The cellular levels of coenzyme Q10 and prosaposin were recovered by treatment with 4-hydroxybenzoquinone, a substrate for coenzyme Q10 synthesis that counteracts the effect of 4-nitrobenzoate. Furthermore, the ganglioside levels were altered in 4-nitrobenzoate treated cells. These results imply that long-term coenzyme Q10 deficiency reduces cellular prosaposin levels and disturbs glycosphingolipid metabolism.