Vitamin B12 inhibits peptidylarginine deiminases and ameliorates rheumatoid arthritis in CAIA mice

• Published in: Biochemical and biophysical research communications Vol. 704; p. 149668
• Main Authors: Yang, Cheng-Wei, Hsu, Hsing-Yu, Lee, Yue-Zhi, Lee, Shiow-Ju
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.04.2024
• Subjects: Arginine; B12; Citrullination; Citrulline; Cobalamin; Peptidylarginine deiminase; Rheumatoid arthritis; Citrullination; Cobalamin; Peptidylarginine deiminase; TNFα; B12; NSAID; CAIA; Citrulline; ACPA; IL-6; ACCP; PADI; Arginine; Rheumatoid arthritis; ANAX2; IL17A
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.149668

Rheumatoid arthritis is an autoimmune disease whose early onset correlates with dysregulated citrullination, a process catalyzed by peptidylarginine deiminase isoform 4 (PADI-4). Here, we report that PADI-4 is a novel target of vitamin B12, a water-soluble vitamin that serves as a cofactor in DNA synthesis and the metabolism of fatty and amino acids. Vitamin B12 preferentially inhibited PADI-4 over PADI-2 with comparable inhibitory activity to the reference compound Cl-amidine in enzymatic inhibition assays, and reduced total cellular citrullination levels including that of histone H3 citrullination mediated by PADI-4. We also demonstrated that hydroxocobalamin, a manufactured form of vitamin B12, significantly ameliorated the severity of collagen type II antibody induced arthritis (CAIA) in mice and diminished gene expression of the rheumatoid inflammatory factors and cytokines IL17A, TNFα, IL-6, COX-II and ANXA2, as well PADI-4. Therefore, the use of vitamin B12 to treat rheumatoid arthritis merits further study. •Vitamin B12 inhibits the enzymatic activities of peptidylarginine deiminase isoforms 2 and 4.•Vitamin B12 diminishes induced cellular citrullinated events.•Vitamin B12 decreases induced cellular citrullinated histone H3.•Vitamin B12 ameliorates the severity of murine CAIA.•Vitamin B12 diminishes the induction of inflammatory factors and cytokines in murine CAIA.