The Biological Axis of Protein Arginine Methylation and Asymmetric Dimethylarginine

Fulton, Melody D.; Brown, Tyler; Zheng, Yu

doi:10.3390/ijms20133322

Cited by 59 publications

(38 citation statements)

References 116 publications

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“…To date, a de novo synthetic pathway of N-monomethylarginine (NMMA), ADMA, or SDMA from free Arg has not been documented. Therefore, free methylarginines found in plasma and cells would derive solely from protein turnover and degradation of proteins containing methylarginines [ 129 ]. By using a comprehensive metabolomic analysis, significantly higher levels of ADMA and SDMA were found in the plasma of RA patients as compared to healthy controls [ 109 ].…”

Section: Arginine Metabolism and Ramentioning

confidence: 99%

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

et al. 2020

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In mammals, amino acid metabolism has evolved to act as a critical regulator of innate and adaptive immune responses. Rheumatoid arthritis (RA) is the most common form of inflammatory arthropathy sustained by autoimmune responses. We examine here the current knowledge of tryptophan and arginine metabolisms and the main immunoregulatory pathways in amino acid catabolism, in both RA patients and experimental models of arthritis. We found that l-tryptophan (Trp) metabolism and, in particular, the kynurenine pathway would exert protective effects in all experimental models and in some, but not all, RA patients, possibly due to single nucleotide polymorphisms in the gene coding for indoleamine 2,3-dioxygenase 1 (IDO1; the enzyme catalyzing the rate-limiting step of the kynurenine pathway). The function, i.e., either protective or pathogenetic, of the l-arginine (Arg) metabolism in RA was less clear. In fact, although immunoregulatory arginase 1 (ARG1) was highly induced at the synovial level in RA patients, its true functional role is still unknown, possibly because of few available preclinical data. Therefore, our analysis would indicate that amino acid metabolism represents a fruitful area of research for new drug targets for a more effective and safe therapy of RA and that further studies are demanding to pursue such an important objective.

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Section: Arginine Metabolism and Ramentioning

confidence: 99%

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

et al. 2020

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“…Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to a family of enzymes known as protein arginine methyltransferases (PRMTs) that catalyze the methylation of arginine residues on target proteins, thereby altering intracellular processes ( Bedford and Clarke, 2009 ; Yang and Bedford, 2013 ; Guccione and Richard, 2019 ; Fulton et al., 2019 ). All nine PRMTs synthesize monomethylarginine (MMA), whereas type I (i.e., PRMT1, PRMT2, PRMT3, CARM1, PRMT6, PRMT8) and type II (i.e., PRMT5, PRMT9) PRMTs deposit asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) marks, respectively, on their target molecules.…”

Section: Introductionmentioning

confidence: 99%

“…Arginine methylation is an underappreciated post-translational modification that occurs with the same frequency as the more widely studied and better understood phosphorylation and ubiquitination events ( Larsen et al., 2016 ). CARM1 employs S-adenosyl-L-methionine to methylate arginine residues in proline-rich motifs of histones and non-histone proteins to mediate critical functions such as signal transduction, DNA repair, transcriptional control, mRNA splicing, and protein translocation ( Bedford and Clarke, 2009 ; Yang and Bedford, 2013 ; Guccione and Richard, 2019 ; Fulton et al., 2019 ). For instance, CARM1 methylates histone H3 at Arg17 and co-activates transcription factor EB (TFEB) to promote the expression of autophagy-related genes ( Shin et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

CARM1 Regulates AMPK Signaling in Skeletal Muscle

Stouth

vanLieshout

et al. 2020

iScience

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Summary Coactivator-associated arginine methyltransferase 1 (CARM1) is an emerging mediator of skeletal muscle plasticity. We employed genetic, physiologic, and pharmacologic approaches to determine whether CARM1 regulates the master neuromuscular phenotypic modifier AMP-activated protein kinase (AMPK). CARM1 skeletal muscle-specific knockout (mKO) mice displayed reduced muscle mass and dysregulated autophagic and atrophic processes downstream of AMPK. We observed altered interactions between CARM1 and AMPK and its network, including forkhead box protein O1, during muscle disuse. CARM1 methylated AMPK during the early stages of muscle inactivity, whereas CARM1 mKO mitigated progression of denervation-induced atrophy and was accompanied by attenuated phosphorylation of AMPK targets such as unc-51 like autophagy-activating kinase 1 Ser555 . Lower acetyl-coenzyme A corboxylase Ser79 phosphorylation, as well as reduced peroxisome proliferator-activated receptor-γ coactivator-1α, was also observed in mKO animals following acute administration of the direct AMPK activator MK-8722. Our study suggests that targeting CARM1-AMPK interplay may have broad impacts on neuromuscular health and disease.

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“…However, the existing data indicate that high NO concentrations may lead to the methylation of nuclear proteins through S-nitrosylation of enzymes termed protein-arginine methyltransferases (PRMTs) [37]. The product of degradation of these proteins, which is catalyzed by PRMTs, is ADMA, an endogenous inhibitor of eNOS [38,39]. The above data may explain the high ADMA concentrations observed in this study in the serum of patients with mandibular fractures before the procedure and 1 day after the procedure, as well as the correlation demonstrated between the concentrations of NO and ADMA.…”

Section: Discussionmentioning

confidence: 99%

Levels of Biological Markers of Nitric Oxide in Serum of Patients with Mandible Factures

Ratajczak–Wrona

Woźniak

Borys

et al. 2020

Preprint

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Background Nitric oxide is a small gaseous molecule with significant bioactivity. It has been observed that NO may have a dual role dependent on its production and concentrations in the bone microenvironment. The objective of the study was to assess the concentration of total nitric oxide malonyldialdehyde, nitrotyrosine, and asymmetric dimethylarginine in the serum of patients with mandibular fractures and to understand the relationship between these compounds, in order to expand the knowledge base of the role of nitric oxide and its activity indicators in the process of bone fracture healing.Material and methods The study included patients with mandibular fractures who were undergoing inpatient and outpatient treatments. Results were analyzed with respect to the measurement time. Total nitric oxide concentration in the blood serum was determined according to the Griess reaction, while the concentration of malonyldialdehyde, nitrotyrosine, and asymmetric dimethylarginine was estimated using the immunoenzymatic method (i.e. enzyme-linked immunosorbent assay).Results Before procedure as well as on the first day and 2 and 6 weeks after the procedure, higher concentrations of total nitric oxide and lower concentrations of malonyldialdehyde were observed in the blood serum of patients with mandibular fractures compared to the control group. No statistically significant differences were found in nitrotyrosine concentrations in the blood serum of patients throughout the measurement period. However, a significantly higher asymmetric dimethylarginine concentration was observed in the patient serum before the procedure and on the first day of operation as compared with the control group. Analysis of the results observed in patient serum with respect to the number of fractures within the mandible demonstrated the same trend of concentrations for the tested compounds for the entire study group.Conclusions In summary, our results revealed that the intensity of local processes resulting from mandibular fractures is associated with the concentration of nitric oxide, confirming its significant role, as well as that of its indicators, in the process of bone fracture healing in this patient population.

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The Biological Axis of Protein Arginine Methylation and Asymmetric Dimethylarginine

Cited by 59 publications

References 116 publications

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

CARM1 Regulates AMPK Signaling in Skeletal Muscle

Levels of Biological Markers of Nitric Oxide in Serum of Patients with Mandible Factures

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