Plasma Homocysteine Concentration is Associated with the Expression Level of Folate Receptor 3

Folic acid and folate receptors (FOLRs) play an important role in the downregulation of homocysteine (Hcy), a risk factor of Alzheimer’s disease, thrombosis, neuropsychiatric illness and fractures. While several studies have reported that FOLR1 and FOLR2 import folic acid into cells, the role of FOL...

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Published in:Scientific Reports Vol. 10; no. 1; p. 10283
Main Authors: Yoshitomi, Ren, Nakayama, Kai, Yamashita, Shuya, Kumazoe, Motofumi, Lin, Ting-An, Mei, Chen-Yi, Marugame, Yuki, Fujimura, Yoshinori, Maeda-Yamamoto, Mari, Kuriyama, Shinichi, Tachibana, Hirofumi
Format: Journal Article
Language:English
Published: London Springer Science and Business Media LLC 24.06.2020
Nature Publishing Group UK
Nature Publishing Group
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ISSN:2045-2322, 2045-2322
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Summary:Folic acid and folate receptors (FOLRs) play an important role in the downregulation of homocysteine (Hcy), a risk factor of Alzheimer’s disease, thrombosis, neuropsychiatric illness and fractures. While several studies have reported that FOLR1 and FOLR2 import folic acid into cells, the role of FOLR3 remains unknown. In this study, we evaluated the impact of FOLR3 on the metabolism of Hcy alongside its protective effect against homocysteine-induced neurotoxicity. To reveal the role of FOLR3, we constructed FOLR3-overexpressed HEK293 cells (FOLR3 + cells) and evaluated cell growth, folic acid intake and Hcy-induced neurotoxicity. Subjects with a high expression of FOLR3 exhibited low levels of plasma homocysteine. The ectopic expression of FOLR3 enhanced cell growth, and the enhanced effect was neutralised by folic acid-deficient media. The Western blot analysis revealed that FOLR3 is secreted into cell supernatant. The folic acid intake of FOLR3 + cells was higher than that of wild-type cells. Supernatant from FOLR3 + cells showed a protective effect on Hcy-induced cytotoxicity. FOLR3 expression in plasma is negatively correlated with plasma homocysteine. Our study emphasizes the role of FOLR3 in the intake of folic acid into cells on the one hand and its protective role in Hcy-induced cytotoxicity on the other.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-67288-9