Homocitrullination

Post-translational modifications (PTMs) influence cellular processes and consequently, their dysregulation is related to the etiologies of numerous diseases. It is widely known that a variety of autoimmune responses in human diseases depend on PTMs of self-proteins. In this review we summarize the latest findings about the role of PTMs in the generation of autoimmunity and, specifically, we address the most relevant PTMs in rheumatic diseases that occur in synovial tissue. Citrullination, homocitrullination (carbamylation) and acetylation are responsible for the generation of Anti-Modified Protein/Peptide Antibodies (AMPAs family), autoantibodies which have been implicated in the etiopathogenesis, diagnosis and prognosis of rheumatoid arthritis (RA)...

BACKGROUND: The bacterial and metabolic networks in immunoglobin A nephropathy (IgAN), the most common type of primary chronic glomerulonephritis worldwide, have not been extensively studied. To help develop better methods for the diagnosis, treatment, and prognosis of IgAN, we characterized the alterations of the urinary microbiome and serum metabolome in patients with IgAN. METHODS: We analyzed serum and urine samples from Chinese patients with IgAN and healthy controls (HCs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 16S ribosomal RNA gene sequencing...

BACKGROUND: The yield and quality of Pugionium cornutum (L.) Gaertn., a healthy, green vegetable with low sugar and high protein contents and high medicinal value, is severely affected by autotoxicity, which is a leading factor in the formation of plant disease. To help characterize the autotoxicity mechanism of P. cornutum (L.) Gaertn., we performed transcriptomic and metabolic analysis of the roots of P. cornutum (L.) Gaertn. response to phthalic acid, an autotoxin from P. cornutum (L...

In recent years, the relationship between Lycium ruthenicum Murr. anthocyanins (LRA) and health has attracted increasing attention. The purpose of this study is to investigate the anti-aging effect and mechanism of LRA through a D-galactose (DG)-induced aging rat model. Our results showed that the long-term intake of LRA, for 8 weeks, improved motor function, reduced serum aging markers, promoted the endogenous antioxidant system, and suppressed the serum inflammatory cytokines in aging rats. Besides, the LRA treatment alleviated DG-induced liver injuries by relieving the inflammation and inhibiting Fas/FasL-mediated cell death...

Use of formula feed (FF) for silkworms for all instars, has promoted transformation and progress in traditional sericulture. However, the cocoon yield of FF silkworms has failed to reach that of silkworms fed mulberry leaves (ML). The biological mechanisms underlying this phenomenon have not been well described. This study aimed to identify metabolic mechanisms and potential biomarkers relating to the poor cocoon yield of FF silkworms. In this study, silkworms received treatments of either ML (ML group) or FF (FF group) for all instars...

BACKGROUND: Maternal prepregnancy obesity is an important risk factor for offspring obesity, which may partially operate through prenatal programming mechanisms. OBJECTIVES: The study aimed to systematically identify prenatal metabolomic profiles mediating the intergenerational transmission of obesity. METHODS: We included 450 African American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) pregnancy cohort...

BACKGROUND: Metabolomic profiling in individuals with chronic kidney disease (CKD) has the potential to identify novel biomarkers and provide insight into disease pathogenesis. METHODS: We examined the association between blood metabolites and CKD progression, defined as the subsequent development of end-stage renal disease (ESRD) or estimated glomerular filtrate rate (eGFR) halving, in 1773 participants of the Chronic Renal Insufficiency Cohort (CRIC) study, 962 participants of the African American Study of Kidney Disease and Hypertension (AASK), and 5305 participants of the Atherosclerosis Risk in Communities (ARIC) study...

BACKGROUND: Bleeding diatheses, common among patients with ESKD, can lead to serious complications, particularly during invasive procedures. Chronic urea overload significantly increases cyanate concentrations in patients with ESKD, leading to carbamylation, an irreversible modification of proteins and peptides. METHODS: To investigate carbamylation as a potential mechanistic link between uremia and platelet dysfunction in ESKD, we used liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to quantify total homocitrulline, and biotin-conjugated phenylglyoxal labeling and Western blot to detect carbamylated integrin α IIb β 3 (a receptor required for platelet aggregation)...

We previously observed the beneficial role of folic acid supplemented from maternal or offspring diet on lamb growth performance and immunity. Twenty-four Hu lambs from four groups (mother received folic acid or not, offspring received folic acid or not) were used in the current study, which was conducted consecutively to elucidate the molecular regulatory mechanisms of folic acid in lambs by analyzing blood metabolome, liver transcriptome, and muscle transcriptome. Serum metabolomics analysis showed that L-homocitrulline, hyodeoxycholic acid, 9-Hpode, palmitaldehyde, N-oleoyl glycine, hexadecanedioic acid, xylose, 1,7-dimethylxanthine, nicotinamide, acetyl-N-formyl-5-methoxykynurenamine, N6-succinyl adenosine, 11-cis-retinol, 18-hydroxycorticosterone, and 2-acetylfuran were down-regulated and methylisobutyrate was up-regulated by the feeding of folic acid from maternal and/or offspring diets...

BACKGROUND: The pathophysiology of sarcopenia is complex and multifactorial; however, it has not yet been fully elucidated. Identifying metabolomic profiles may help clarify the mechanisms underlying sarcopenia. OBJECTIVE: This pilot study explored potential noninvasive biomarkers of severe sarcopenia through metabolomic analysis in community-dwelling older men. METHODS: Twenty older men (mean age: 81.9 ± 2.8 years) were selected from the Korean Frailty and Aging Cohort Study...

Gyrate atrophy of the choroid and retina (GACR) secondary to deficiency of ornithine aminotransferase (OAT) is a rare autosomal recessive metabolic disorder usually diagnosed in childhood when patients develop myopia and a characteristic retinal degeneration accompanied by hyperornithinemia. Plasma ammonia is normal or sub-normal after the neonatal period. A few GACR patients present in early infancy with hyperammonemia, encephalopathy and a biochemical profile of low plasma ornithine, citrulline and arginine, with increased urinary excretion of homocitrulline and orotic acid, resembling a primary urea cycle disorder...

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high mortality rate due to its poor diagnosis in the early stage. Here, we report a urinary metabolomic study on a cohort of CRC patients ( n  =67) and healthy controls ( n  =21) using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Pathway analysis showed that a series of pathways that belong to amino acid metabolism, carbohydrate metabolism, and lipid metabolism were dysregulated, for instance the glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glycolysis, and TCA cycle...

Objective: Hyperargininemia due to Arginase 1 deficiency is a rare inborn error of the urea cycle with an incidence estimated at 1:950 000. It has typical severe and progressive abnormal neurological features with biochemical findings of hyperargininemia and hyperexcretion of orotic acid. The aim of our study is to review the clinical and biochemical presentations of 4 children diagnosed with Arginase 1 deficiency in Malaysia and compare with the literature review. Design and Methods: We retrospectively reviewed the medical records of 4 patients with molecularly confirmed Arginase 1 deficiency...

Homocitrullination is the post translation modification (PTM) of the amino acid lysine to homocitrulline also referred to as carbamylation. This PTM has mainly been studied in relation to autoimmune diseases including rheumatoid arthritis. Homocitrullination of lysines alters their charge which can lead to generation of neoepitopes that are differentially presented by MHC-II and induce modification-specific immune responses. Homocitrullination is often considered a process which triggers autoimmune disease by bypassing self-tolerance however, we suggest that homocitrullination may also have an alternative role in immune responses including protection against cancer...

OBJECTIVE: Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline-containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG...

Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata . This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms...

BACKGROUND: Homocitrullination is the post-translational modification of lysine that is recognized by T cells. METHODS: This study identified homocitrullinated peptides from aldolase, enolase, cytokeratin and binding immunoglobulin protein and used human leukocyte antigen (HLA) transgenic mice to assess immunogenicity by enzyme-linked immunosorbent spot assay. Vaccine efficacy was assessed in tumor therapy studies using HLA-matched B16 melanoma expressing constitutive or interferon γ (IFNγ)-inducible major histocompatibility complex class II (MHC-II) as represented by most human tumors...

BACKGROUND AND AIMS: Abnormalities in lipid metabolism, accumulation of uremic toxins and advanced glycation end products may contribute to worsening atherosclerosis. This study characterized the glycation and carbamoylation profile of serum albumin isolated from individuals with diabetic kidney disease and its influence on cholesterol efflux. MATERIAL AND METHODS: 49 patients with type 2 diabetes (T2DM) and different eGFR evaluated glycation and carbamoylation profile by measurement of carboxymethyl lysine (CML) and carbamoylated proteins (CBL) in plasma by ELISA, homocitrulline (HCit) in plasma by colorimetry...

Backgrounds: Nonalcoholic fatty liver disease (NAFLD) has multiple causes, is triggered by individual genetic susceptibility, environmental factors, and metabolic disturbances, and may be triggered by acquired metabolic stress. The metabolic profiles of NAFLD show significant ethnic differences, and the metabolic characteristics of NAFLD in Chinese individuals are unclear. Our study aimed to identify the metabolites and pathways associated with NAFLD in a Chinese cohort. Methods: One hundred participants, including 50 NAFLD patients and 50 healthy controls, were enrolled in this retrospective observational study at Jinling Hospital in Nanjing; serum samples were collected from the patients and healthy subjects...

Derivatization of amino acids by 2 M HCl/CH3 OH (60 min, 80 °C) followed by derivatization of the intermediate methyl esters with pentafluoropropionic anhydride (PFPA) in ethyl acetate (30 min, 65 °C) is a useful two-step derivatization procedure (procedure A) for their quantitative measurement in biological samples by gas chromatography-mass spectrometry (GC-MS) as methyl ester pentafluoropropionic (PFP) derivatives, (Me)m -(PFP)n . This procedure allows in situ preparation of trideutero-methyl esters PFP derivatives, (d3 Me)m -(PFP)n , from synthetic amino acids and 2 M HCl/CD3 OD for use as internal standards...