GC-MS and LC-MS/MS pilot studies on the guanidine (NG)-dimethylation in native, asymmetrically and symmetrically NG-dimethylated arginine-vasopressin peptides and proteins in human red blood cells

Bollenbach, Alexander; Gambaryan, Stepan; Mindukshev, Igor; Pich, Andreas; Tsikas, Dimitrios

doi:10.1016/j.jchromb.2020.122024

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…Protein-arginine dimethylation is a major post-translational modification (PTM) (Scheme 1 ). Arginine-moieties of numerous proteins in histones and other molecular structures are methylated by PRMT in many tissues and cells, notably in red blood cells (Bollenbach et al 2020a ; b ). The physiological importance of arginine-dimethylated proteins is currently of major scientific interest (Greer and Shi 2012 ; Blanc and Richard 2017 ; Peng and Wong 2017 ; Beltran-Alvarez et al 2011 , 2014 , 2015 ; Samuel et al 2021 ; Sirover 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we performed similar analyses for DMA + ADMA, DMA + ADMA + SDMA, and (DMA + ADMA)/SDMA. These composites were found to be useful measures of the whole-body asymmetric, asymmetric and symmetric dimethylation, and of the balance of asymmetric-to-symmetric dimethylation of arginine residues in proteins (Bollenbach et al 2020a ; b ). After successful re-evaluation of a previously reported validated GC–MS method for DMA (Tsikas et al 2007 ), we applied this method in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Measurement of major urinary metabolites of circulating precursors is a widely used non-invasive approach to estimate their whole-body synthesis of endogenous substances such as DMA (Achan et al 2003 ; Tsikas 2020 and references therein), nitrate (Baylis and Vallance 1998 ), prostaglandins (Ferretti et al 1983 ), thromboxane (Roberts et al 1977 ), leukotrienes (reviewed in Tsikas 1998 ), RNA (Sander et al 1986 ), and catecholamines (Duncan et al 1988 ). Recently, we proposed such a method to measure whole-body PADiMe activity in humans and demonstrated its utility in human studies (Bollenbach et al 2019 ; Bollenbach et al 2020a , b ). PADiMe activity indices (PADiMeX) include urinary DMA, ADMA, SDMA and their composites, with the index DMA + ADMA reflecting asymmetric PADiMe activity (aPADiMeX), the index DMA + ADMA + SDMA reflecting total PADiMe activity (toPADiMeX), and the index (DMA + ADMA)/SDMA reflecting the balance between asymmetric and symmetric PADiMe activities (a/sPADiMeX) (Bollenbach et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

et al. 2021

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Arginine residues in proteins can be singly or doubly methylated post-translationally. Proteolysis of arginine-methylated proteins provides monomethyl arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). ADMA and SDMA are considered cardiovascular risk factors, with the underlying mechanisms being not yet fully understood. SDMA lacks appreciable metabolism and is almost completely eliminated by the kidney, whereas ADMA is extensively metabolized to dimethylamine (DMA), with a minor ADMA fraction of about 10% being excreted unchanged in the urine. Urinary DMA and ADMA are useful measures of whole-body asymmetric arginine-dimethylation, while urinary SDMA serves as a whole-body measure of symmetric arginine-dimethylation. In renal transplant recipients (RTR), we previously found that higher plasma ADMA concentrations and lower urinary ADMA and SDMA concentrations were associated with a higher risk of all-cause mortality. Yet, in this RTR collective, no data were available for urinary DMA. For the present study, we additionally measured the excretion rate of DMA in 24-h collected urine samples of the RTR and of healthy kidney donors in the cohort, with the aim to quantitate whole-body asymmetric (ADMA, DMA) and symmetric (SDMA) arginine-dimethylation. We found that lower DMA excretion rates were associated with higher all-cause mortality, yet not with cardiovascular mortality. In the healthy donors, kidney donation was associated with considerable decreases in ADMA (by − 39%, P < 0.0001) and SDMA (by − 21%, P < 0.0001) excretion rates, yet there was no significant change in DMA (by − 9%, P = 0.226) excretion rate. Our results suggest that protein-arginine dimethylation is altered in RTR compared to healthy kidney donors and that it is pronouncedly shifted from symmetric to asymmetric arginine-dimethylation, with whole-body protein-arginine dimethylation being almost unaffected.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

et al. 2021

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“…Conditions where erythrocytes adhere to the endothelium can result in hypertension and vasoconstriction. Major erythrocytic membrane proteins, which include spectrin-α, spectrin-β, ankyrin-1, and protein band 4.1, are Arg-dimethylated proteins [63]. Altered erythrocyte membrane protein composition has been shown to mirror the pleiotropic effects of hypertension susceptibility genes and disease pathogenesis [64].…”

Section: Discussionmentioning

confidence: 99%

An Ethnic Comparison of Arginine Dimethylation and Cardiometabolic Factors in Healthy Black and White Youth: The ASOS and African-PREDICT Studies

Bollenbach

Schutte

Kruger

et al. 2020

JCM

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Proteinic arginine dimethylation (PADiMe) is a major post-translational modification. Proteolysis of asymmetric and symmetric PADiMe products releases asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), respectively, two endogenous atherogenic substances. SDMA, ADMA, and its major metabolite dimethylamine (DMA) are eliminated by the kidney. The urinary concentrations of DMA+ADMA, SDMA, and DMA+ADMA+SDMA are useful measures of the whole-body asymmetric and symmetric PADiMe, respectively. Urinary (DMA+ADMA)/SDMA is an index of the asymmetric to symmetric PADiMe balance. In two bi-ethnic studies, the ASOS (39 black boys, 41 white boys) and the African-PREDICT (292 black young men, 281 white young men) studies, we investigated whether ethnicity is a major determinant of PADiMe, and whether PADiMe is associated with blood pressure and ethnicity-dependent growth and inflammatory factors, including HDL. DMA, ADMA, and SDMA were measured in spot urine samples by gas chromatography–mass spectrometry, and their excretion was corrected for creatinine excretion. In black boys, creatinine-corrected DMA, DMA+ADMA, and DMA+ADMA+SDMA concentrations were lower by 11.7%, 9.5%, and 7.6% (all p < 0.05), respectively, compared to the white boys, and 3.4%, 2.0%, and 1.8% lower (all p < 0.05), respectively, in black compared to white men. (DMA+ADMA)/SDMA did not differ between black boys and black men, but was higher in white boys compared to white men. ADMA did not differ between black and white boys, or between black and white men. Creatinine-corrected SDMA excretion was lower in black boys compared to white boys (by 8%) and to white men (by 3.1%). None of the PADiMe indices were associated with blood pressure in either study. IGF-binding protein 3 correlated inversely with all PADiMe indices in the black men only. Our study showed that asymmetric proteinic arginine dimethylation is higher in white boys than in black boys, and that this difference disappears in adulthood. ADMA metabolism and SDMA excretion were lower in the black subjects compared to the white subjects, suggesting ethnicity-dependent hepatic and renal elimination of ADMA and SDMA in the childhood. The results of our study may have clinical relevance beyond atherosclerosis, such as in growth and inflammation, which have not been sufficiently addressed thus far.

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“…Bollenbach et al observed that main sources of methylarginines include proteins responsible for the stability of erythrocyte membrane spectrin-α, spectrin-β and protein 4.1. The same study observed that methylated arginine can change protein function and some peptide chains with methylated arginine induced platelet aggregation [ 117 ].…”

Section: Erythrocytesmentioning

confidence: 99%

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

Mochol

Gawryś

Gajecki

et al. 2021

IJMS

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Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial dysfunction. Nevertheless, not much is known about blood components, which justifies the current review. This review focuses on molecular mechanisms triggered by sleep apnea. The recurrent periods of hypoxemia followed by reoxygenation promote reactive oxygen species (ROS) overproduction and increase inflammatory response. In this review paper we also intend to summarize the effect of treatment with continuous positive airway pressure (CPAP) on changes in the profile of the endothelial function and its subsequent potential clinical advantage in lowering cardiovascular risk in other comorbidities such as diabetes, atherosclerosis, hypertension, atrial fibrillation. Moreover, this paper is aimed at explaining how the presence of OSA may affect platelet function and exert effects on rheological activity of erythrocytes, which could also be the key to explaining an increased risk of stroke.

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GC-MS and LC-MS/MS pilot studies on the guanidine (NG)-dimethylation in native, asymmetrically and symmetrically NG-dimethylated arginine-vasopressin peptides and proteins in human red blood cells

Cited by 5 publications

References 43 publications

Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

An Ethnic Comparison of Arginine Dimethylation and Cardiometabolic Factors in Healthy Black and White Youth: The ASOS and African-PREDICT Studies

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

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