Title | Vitamin E Deficiency Dysregulates Amino Acids and Methyl Donor Compounds During Zebrafish Embryogenesis |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Zhang, J, Head, B, Leonard, SW, Choi, J, Tanguay, RL, Traber, M |
Journal | Redox Biology |
Pagination | 101784 |
Date Published | 11/2020 |
ISSN | 22132317 |
Abstract | Highlights
Vitamin E (α-tocopherol, VitE) was discovered as a nutrient essential to protect fetuses, but its molecular role in embryogenesis remains undefined. We hypothesize that the increased lipid peroxidation due to VitE deficiency drives a complex mechanism of overlapping biochemical pathways needed to maintain glutathione (GSH) homeostasis that is dependent on betaine and its methyl group donation. We assess amino acids and thiol changes that occur during embryogenesis [12, 24 and 48 hours post fertilization (hpf)] in VitE-sufficient (E+) and deficient (E–) embryos using two separate, novel protocols to quantitate changes using UPLC-MS/MS. Using partial least squares discriminant analysis, we found that betaine is a critical feature separating embryos by VitE status and is higher in E– embryos at all time points. Other important features include: glutamic acid, increased in E– embryos at 12 hpf; choline, decreased in E– embryos at 24 hpf; GSH, decreased in E– embryos at 48 hpf. By 48 hpf, GSH was significantly lower in E– embryos (P < 0.01), as were both S-adenosylmethionine (SAM, P < 0.05) and S-adenosylhomocysteine (SAH, P < 0.05), while glutamic acid was increased (P < 0.01). Since GSH synthesis requires cysteine (which was unchanged), these data suggest that both the conversion of homocysteine and the uptake of cystine via the Xc– exchanger are dysregulated. Our data clearly demonstrates the highly inter-related dependence of methyl donors (choline, betaine, SAM) and the methionine cycle for maintenance of thiol homeostasis. Additional quantitative flux studies are needed to clarify the quantitative importance of these routes.
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DOI | 10.1016/j.redox.2020.101784 |
Short Title | Redox Biology |