Reduced prosaposin levels in HepG2 cells with long-term coenzyme Q10 deficiency

Glycosphingolipids are involved in intercellular signaling, adhe­sion, 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 d...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Clinical Biochemistry and Nutrition 2022, Vol.71(2), pp.97-102
Main Authors: Takeuchi, Hikaru, Sugawara, Kyosuke, Okamoto, Mizuho, Nakamura, Akari, Tanaka, Tsukika, Fujita, Yui, Ishiguro, Kaiho, Yamazaki, Hana, Okada, Maiko, Mikami, Akane, Fujisawa, Akio, Yamamoto, Yorihiro, Kashiba, Misato
Format: Article
Language:English
Subjects:
4-nitrobenzoate
Aging
Biosynthesis
Coenzyme Q10
Cofactors
Electron transport
Glycosphingolipids
Lipids
Metabolism
Mitochondria
mRNA
Original
prosaposin
Proteins
Substrates
Transportation systems
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Glycosphingolipids are involved in intercellular signaling, adhe­sion, 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.
ISSN:0912-0009
1880-5086
DOI:10.3164/jcbn.21-126