{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T17:51:38Z","timestamp":1774461098147,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K15767"],"award-info":[{"award-number":["19K15767"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20580132"],"award-info":[{"award-number":["20580132"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: Vitamin B12 deficiency in Caenorhabditis elegans results in severe oxidative stress and induces morphological abnormality in mutants due to disordered cuticle collagen biosynthesis. We clarified the underlying mechanism leading to such mutant worms due to vitamin B12 deficiency. (2) Results: The deficient worms exhibited decreased collagen levels of up to approximately 59% compared with the control. Although vitamin B12 deficiency did not affect the mRNA expression of prolyl 4-hydroxylase, which catalyzes the formation of 4-hydroxyproline involved in intercellular collagen biosynthesis, the level of ascorbic acid, a prolyl 4-hydroxylase coenzyme, was markedly decreased. Dityrosine crosslinking is involved in the extracellular maturation of worm collagen. The dityrosine level of collagen significantly increased in the deficient worms compared with the control. However, vitamin B12 deficiency hardly affected the mRNA expression levels of bli-3 and mlt-7, which are encoding crosslinking-related enzymes, suggesting that deficiency-induced oxidative stress leads to dityrosine crosslinking. Moreover, using GMC101 mutant worms that express the full-length human amyloid \u03b2, we found that vitamin B12 deficiency did not affect the gene and protein expressions of amyloid \u03b2 but increased the formation of dityrosine crosslinking in the amyloid \u03b2 protein. (3) Conclusions: Vitamin B12-deficient wild-type worms showed motility dysfunction due to decreased collagen levels and the formation of highly tyrosine-crosslinked collagen, potentially reducing their flexibility. In GMC101 mutant worms, vitamin B12 deficiency-induced oxidative stress triggers dityrosine-crosslinked amyloid \u03b2 formation, which might promote its stabilization and toxic oligomerization.<\/jats:p>","DOI":"10.3390\/ijms222312959","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:28Z","timestamp":1638314548000},"page":"12959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dityrosine Crosslinking of Collagen and Amyloid-\u03b2 Peptides Is Formed by Vitamin B12 Deficiency-Generated Oxidative Stress in Caenorhabditis elegans"],"prefix":"10.3390","volume":"22","author":[{"given":"Kyohei","family":"Koseki","sequence":"first","affiliation":[{"name":"The United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aoi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naho","family":"Okamoto","sequence":"additional","affiliation":[{"name":"The United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Food Quality and Safety, College of Food Science, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-4148","authenticated-orcid":false,"given":"Tomohiro","family":"Bito","sequence":"additional","affiliation":[{"name":"The United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6982-8522","authenticated-orcid":false,"given":"Yukinori","family":"Yabuta","sequence":"additional","affiliation":[{"name":"The United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Kawano","sequence":"additional","affiliation":[{"name":"The United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumio","family":"Watanabe","sequence":"additional","affiliation":[{"name":"The United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan"},{"name":"Department of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biochi.2020.06.014","article-title":"Naturally occurring cobalamin (B12) analogs can function as cofactor for human methylmalonyl-CoA mutase","volume":"183","author":"Sokolovskaya","year":"2021","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jimd.12009","article-title":"Vitamin B12, folate, and the methionine remethylation cycle\u2014Biochemistry, pathways, and regulation","volume":"42","author":"Froese","year":"2018","journal-title":"J. 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