3-nitrotyrosine and Sjogren-s-Syndrome

An involvement of oxidative stress (OS) was found in recent studies of Sjøgren's syndrome (SS) that reported significant changes in protein oxidation, myeloperoxidase activity, TNF-α, nitrotyrosine, and GSH levels in plasma from SS patients. Excess levels of OS markers, as oxidative DNA damage and propanoyl-lysine, were reported in saliva from SS patients. Previous reports concurred with a role of OS in SS pathogenesis, by showing a decreased expression of antioxidant activities in conjunctival epithelial cells of SS patients and in parotid gland tissue samples from SS patients. A link between OS and mitochondrial dysfunction (MDF) is recognized both on the grounds of the established role of mitochondria in reactive oxygen species (ROS) formation and by the occurrence of MDF in a set of OS-related disorders. Earlier studies detected mitochondrial alterations in cells from SS patients, related to the action of antimitochondrial autoantibodies, and affecting specific mitochondrial activities. Thus, a link between MDF and OS may be postulated in SS, prompting studies aimed at elucidating SS pathogenesis and in the prospect of chemoprevention trials in SS clinical management.

Topics: Biomarkers; Chemoprevention; DNA Damage; Glutathione; Humans; Mitochondria; Oxidative Stress; Peroxidase; Saliva; Sjogren's Syndrome; Tumor Necrosis Factor-alpha; Tyrosine

Primary Sjögren's syndrome (SS) shares clinical and serologic features with rheumatoid arthritis and systemic lupus erythematosus, 2 diseases characterized by acceleration of atherosclerosis. Signs of precocious atherosclerosis have also been shown in SS, although the pathogenic basis of early arterial damage is unclear. The arterial wall was functionally evaluated in SS subjects with analysis of the role played by disease-related factors.. Endothelium-dependent flow-mediated vasodilation (FMV) and endothelium-independent nitrate-mediated vasodilation (NMV) were evaluated in 45 women with SS and 59 age-matched female controls. In addition, serum soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 (VCAM-1), and nitrotyrosine were detected.. Although patient FMV values did not differ from those of control subjects (mean +/- SD 7.4 +/- 3.6 versus 7.7 +/- 1.9; not significant), NMV was lower in SS patients than in controls (mean +/- SD 8.1 +/- 3.5 versus 10.3 +/- 2.1; P

Topics: Adult; Atherosclerosis; Brachial Artery; Case-Control Studies; Endothelium, Vascular; Female; Humans; Intercellular Adhesion Molecule-1; Matched-Pair Analysis; Middle Aged; Reference Values; Sjogren's Syndrome; Statistics, Nonparametric; Tyrosine; Vascular Cell Adhesion Molecule-1; Vasodilation

To demonstrate the existence of oxidative stress and the role of the antioxidant thioredoxin (TRX) in Sjögren's syndrome (SS).. Labial biopsy specimens from patients with SS were analyzed immunohistochemically to detect 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), nitrotyrosine, and TRX. Levels of TRX in saliva and plasma were quantified by ELISA. To analyze the effect of TRX on human salivary gland (HSG) cells, recombinant TRX (rTRX)-treated HSG cells were stimulated by interferon-gamma (IFN-gamma) for detecting interleukin 6 (IL-6) with ELISA and RT-PCR, or stimulated with IFN-gamma and anti-Fas antibody for analyzing Fas-induced apoptosis with PI/annexin V staining.. Large amounts of 8-OHdG, 4-HNE, nitrotyrosine, and TRX were produced in salivary duct cells of SS patients, whether there was periductal lymphocytic infiltration or not. Strong TRX expression was detected in acinar cells from 13 of 19 SS specimens. Levels of salivary TRX were significantly higher in SS patients than in controls (p < 0.05), and were inversely related to the salivary flow rates in SS patients. Patients who showed acinar TRX expression had higher salivary TRX levels than those who did not (p < 0.05). Interferon-gamma-induced expression of IL-6 and Fas-mediated apoptosis in HSG cells were significantly suppressed by pretreating cells with rTRX.. Parallel production of oxidative stress markers together with massive secretion of TRX suggests that oxidative stress induces TRX in the salivary gland. Moreover, suppression of IL-6 production and apoptosis by rTRX in HSG cells suggests TRX acts to protect the salivary glands of SS patients from tissue damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aldehydes; Antioxidants; Apoptosis; Biomarkers; Cysteine Proteinase Inhibitors; Deoxyguanosine; Female; Humans; Hydrogen Peroxide; Interferon-gamma; Interleukin-6; Middle Aged; Oxidants; Oxidative Stress; Saliva; Salivary Glands; Sjogren's Syndrome; Thioredoxins; Tyrosine