High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans
Using Caenorhabditis elegans as a model animal, we evaluated the effects of chronical supplementation with high-dose folic acid on physiological events such as life cycle and egg-laying capacity and folate metabolism. Supplementation of high-dose folic acid significantly reduced egg-laying capacity....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720309290 |
| _version_ | 1819060752433020928 |
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| author | Kyohei Koseki Yukina Maekawa Tomohiro Bito Yukinori Yabuta Fumio Watanabe |
| author_facet | Kyohei Koseki Yukina Maekawa Tomohiro Bito Yukinori Yabuta Fumio Watanabe |
| author_sort | Kyohei Koseki |
| collection | DOAJ |
| description | Using Caenorhabditis elegans as a model animal, we evaluated the effects of chronical supplementation with high-dose folic acid on physiological events such as life cycle and egg-laying capacity and folate metabolism. Supplementation of high-dose folic acid significantly reduced egg-laying capacity. The treated worms contained a substantial amount of unmetabolized folic acid and exhibited a significant downregulation of the mRNAs of cobalamin-dependent methionine synthase reductase and 5,10-methylenetetrahydrofolate reductase. In vitro experiments showed that folic acid significantly inhibited the activity of cobalamin-dependent methionine synthase involved in the metabolism of both folate and methionine. In turn, these metabolic disorders induced the accumulation of unmetabolized homocysteine, leading to severe oxidative stress in worms. These results were similar to the phenomena observed in mammals during folate deficiency. |
| first_indexed | 2024-12-21T14:31:59Z |
| format | Article |
| id | doaj.art-1a68c289e38443f39ac69919bfe1f202 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-21T14:31:59Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-1a68c289e38443f39ac69919bfe1f2022022-12-21T19:00:26ZengElsevierRedox Biology2213-23172020-10-0137101724High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegansKyohei Koseki0Yukina Maekawa1Tomohiro Bito2Yukinori Yabuta3Fumio Watanabe4The United Graduate School of Agricultural Sciences, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, JapanGraduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, JapanThe United Graduate School of Agricultural Sciences, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, Japan; Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, JapanThe United Graduate School of Agricultural Sciences, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, Japan; Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, JapanThe United Graduate School of Agricultural Sciences, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, Japan; Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, Japan; Corresponding author. The United Graduate School of Agricultural Sciences, Tottori University, 4Koyama-Minami, Tottori city, Tottori, 680-8553, Japan.Using Caenorhabditis elegans as a model animal, we evaluated the effects of chronical supplementation with high-dose folic acid on physiological events such as life cycle and egg-laying capacity and folate metabolism. Supplementation of high-dose folic acid significantly reduced egg-laying capacity. The treated worms contained a substantial amount of unmetabolized folic acid and exhibited a significant downregulation of the mRNAs of cobalamin-dependent methionine synthase reductase and 5,10-methylenetetrahydrofolate reductase. In vitro experiments showed that folic acid significantly inhibited the activity of cobalamin-dependent methionine synthase involved in the metabolism of both folate and methionine. In turn, these metabolic disorders induced the accumulation of unmetabolized homocysteine, leading to severe oxidative stress in worms. These results were similar to the phenomena observed in mammals during folate deficiency.http://www.sciencedirect.com/science/article/pii/S2213231720309290Caenorhabditis elegansFolateFolic acidHomocysteineOxidative stress |
| spellingShingle | Kyohei Koseki Yukina Maekawa Tomohiro Bito Yukinori Yabuta Fumio Watanabe High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans Redox Biology Caenorhabditis elegans Folate Folic acid Homocysteine Oxidative stress |
| title | High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans |
| title_full | High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans |
| title_fullStr | High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans |
| title_full_unstemmed | High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans |
| title_short | High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans |
| title_sort | high dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine leading to severe oxidative stress in caenorhabditis elegans |
| topic | Caenorhabditis elegans Folate Folic acid Homocysteine Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2213231720309290 |
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