ABSTRACT
Protein nitrosylation is a ubiquitous post-translational modification in almost all biological systems. However, its function on stem cell biology is so far incompletely understood. Here, we demonstrated that peroxiredoxin 2 (Prdx-2) nitrosylation was involved in cardiomyocyte differentiation of mouse embryonic stem (ES) cells induced by S-nitrosoglutathione (GSNO). We found that temporary GSNO exposure could promote ES cell-derived cardiomyogenesis. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics approach, coupled with biotin switch technique, a total of 104 nitrosylated proteins were identified. Specifically, one of the antioxidant enzymes, Prdx-2, was abundantly nitrosylated and temporarily reduced in antioxidant activity, causing transient endogenous hydrogen peroxide (H2O2) accumulation and subsequent X-box binding protein-1s/phosphatidylinositol 3-kinase pathway activation. The present study reveals the mechanism in which GSNO favors cardiomyocyte differentiation. Prdx-2 nitrosylation could be a potent strategy to affect the pluripotent stem cell-derived cardiomyogenesis.
Subject(s)
Cell Differentiation/genetics , Mouse Embryonic Stem Cells/cytology , Peroxiredoxins/genetics , X-Box Binding Protein 1/genetics , Animals , Hydrogen Peroxide/metabolism , Mice , Mouse Embryonic Stem Cells/metabolism , Myocytes, Cardiac/metabolism , Nitric Oxide/metabolism , Oxidation-Reduction , Peroxiredoxins/metabolism , Phosphatidylinositol 3-Kinases/genetics , Protein Processing, Post-Translational/genetics , Proteomics , S-Nitrosoglutathione/metabolism , Signal TransductionABSTRACT
BACKGROUND AND AIMS: Metabolic syndrome (MetS) comprises central obesity, insulin resistance, hypertension and dyslipidemia, interrelated metabolic risk factors for diabetes and cardiovascular disease. A state of low-grade systemic inflammation may underlie this constellation of risk factors. Chronic inflammatory conditions, such as periodontal disease, may contribute to systemic inflammation and development of MetS. This study examines the association of periodontitis with MetS with and without consideration of systemic inflammatory status. METHODS: The association of alveolar bone loss (none/slight vs moderate/severe) determined from panoramic radiographs and MetS parameters were analyzed using logistic regression, adjusting for age, sex, ethnicity, and smoking in 112 men and 78 women (mean+/-SD age 56.7+/-13.3 and 60.0+/-12.1, respectively) participating in the Baltimore Longitudinal Study of Aging. RESULTS: Participants with radiographic evidence of moderate to advanced alveolar bone loss were significantly more likely to have MetS than those with minimal or no bone loss (OR 2.61, 95% CI 1.1-6.1, p<0.05). No significant differences in systemic inflammation were found between periodontal groups. CONCLUSIONS: The association of alveolar bone loss to MetS is consistent with the hypothesis that destructive periodontal disease may contribute to the development of MetS and elevations in systemic inflammation. Longitudinal studies are necessary to clarify the role of periodontal disease in the development of MetS and conditions associated with chronic inflammation.
