Posttranslational Protein Modification in the Salivary Glands of Sjögren’s Syndrome Patients

Herrera‐Esparza, Rafael; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Badillo-Soto, Martha Adriana; Torres-del-Muro, Felipe; Bollain-y-Goytia, Juan José; Pacheco-Tovar, Deyanira; Avalos‐Díaz, Esperanza

doi:10.1155/2013/548064

Cited by 9 publications

(6 citation statements)

References 32 publications

(26 reference statements)

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“…Citrullination refers to the post-translational conversion of protein arginine residues into citrulline residues, a process catalysed by peptidylarginine deiminases (PADs) 1–4 and PAD6 [ 1 ]. Citrullination plays an important pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) [ 2 , 3 ] and, possibly, in a number of other autoimmune diseases, inflammatory diseases or neurodegenerative conditions, including multiple sclerosis [ 4 ], Alzheimer’s disease [ 5 ], psoriasis [ 6 ], Sjögren’s syndrome [ 7 ], type 1 diabetes [ 8 ] and chronic obstructive pulmonary disease [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase

et al. 2016

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BackgroundCitrullination catalysed by peptidylarginine deiminases (PADs) plays an important pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and, possibly, several other inflammatory diseases. Non-physiological reducing agents such as dithiothreitol (DTT) are normally added to the reaction buffer when determining PAD activity in vitro. We investigated the ability of reduced glutathione (GSH), the most abundant intracellular small-molecule thiol in vivo, to activate PADs.MethodsActivity of recombinant human (rh) PAD2 and PAD4, PADs contained in synovial fluid (SF) samples from RA patients and PADs released from phorbol 12-myristate 13-acetate (PMA)-stimulated cells was measured using an in-house PAD activity assay detecting citrullination of fibrinogen.ResultsNo activity of rhPAD2, rhPAD4 or PADs within SF was observed without addition of an exogenous reducing agent. Activity of both recombinant and SF PAD was observed in the presence of 1 mM DTT or 10–15 mM GSH. Following stimulation with PMA, human isolated leucocytes, but not mononuclear cells, released enzymatically active PAD, the activity of which was abolished upon pre-incubation of the cells with the glutathione reductase inhibitor 2-AAPA. No PAD activity was observed in the corresponding supernatants, but addition of exogenous GSH restored activity.ConclusionsCatalytic activity of PAD requires reducing conditions. GSH meets this requirement at concentrations comparable with those found within cells. Active PAD, reduced by GSH, is released from PMA-stimulated granulocytes, but becomes inactivated in the extracellular space.

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Section: Introductionmentioning

confidence: 99%

Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase

et al. 2016

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“…Previous studies have reported PTM (post-translational modification)-modified proteins in patients with pSS such as citrullinated Ro60 and histone 1 ( 89 ). Furthermore, salivary antibodies against cyclic citrullinated peptide (anti-CCP), a proxy for anti-citrullinated protein antibodies (ACPA), have been identified in patients with pSS ( 90 ), suggesting that citrullinated proteins can be a utilized as diagnostic biomarkers. Liao et al.…”

Section: Resultsmentioning

confidence: 99%

Sjögren’s syndrome: novel insights from proteomics and miRNA expression analysis

Kamounah,

Sembler-Møller,

Nielsen

et al. 2023

Front. Immunol.

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IntroductionSjögren’s syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and ocular dryness. The aetiology of SS remains unclear, and the disease lacks distinctive clinical features. The current diagnostic work-up is complex, invasive and often time-consuming. Thus, there is an emerging need for identifying disease-specific and, ideally, non-invasive immunological and molecular biomarkers that can simplify the diagnostic process, allow stratification of patients, and assist in monitoring the disease course and outcome of therapeutic intervention in SS.MethodsThis systematic review addresses the use of proteomics and miRNA-expression profile analyses in this regard.Results and discussionOut of 272 papers that were identified and 108 reviewed, a total of 42 papers on proteomics and 23 papers on miRNA analyses in saliva, blood and salivary gland tissue were included in this review. Overall, the proteomic and miRNA studies revealed considerable variations with regard to candidate biomarker proteins and miRNAs, most likely due to variation in sample size, processing and analytical methods, but also reflecting the complexity of SS and patient heterogeneity. However, interesting novel knowledge has emerged and further validation is needed to confirm their potential role as biomarkers in SS.

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“…One study investigated the influence of inflammation from periodontal disease using RA-model mice analysis in serum and saliva samples of both anti-citrullinated proteins (using antibody analysis) and citrullinated proteins (using gel electrophoresis) [ 180 ]. Saliva and serum showed similar results, evidencing protein citrullination around the 55 kDa molecular-weight electrophoretic band.…”

Section: Citrullinationmentioning

confidence: 99%

“…Patients affected by Sjögren’s syndrome have been found to be positive for ACPAs and showed increased levels of the PAD 2 enzyme, suggesting a possible role of citrullination in the disease that could be responsive to autoantigens triggering [ 180 ]. However, in the same study, it was outlined that only approximately 7.5% of Sjögren’s syndrome patients are positive for ACPAs.…”

Section: Citrullinationmentioning

confidence: 99%

The Post-Translational Modifications of Human Salivary Peptides and Proteins Evidenced by Top-Down Platforms

Messana

Manconi

Cabras

et al. 2023

IJMS

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In this review, we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. In the beginning, we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section, the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteomes. Three sections are dedicated to the description of glycation and enzymatic glycosylation. Citrullination and N- and C-terminal post-translational modifications (PTMs) and miscellaneous other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed throughout the sections of the manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

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Posttranslational Protein Modification in the Salivary Glands of Sjögren’s Syndrome Patients

Cited by 9 publications

References 32 publications

Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase

Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase

Sjögren’s syndrome: novel insights from proteomics and miRNA expression analysis

The Post-Translational Modifications of Human Salivary Peptides and Proteins Evidenced by Top-Down Platforms

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