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Phosphorylation of Histone H2A.X in Peripheral Blood Mononuclear Cells May Be a Useful Marker for Monitoring Cardiometabolic Risk in Nondiabetic Individuals.

ABSTRACT: Phosphorylation of H2A.X (serine 139) in the histone H2A family located in the downstream of the DNA damage kinase signaling cascade is an important indicator of DNA damage. Recently, phosphorylation of H2A.X was proposed as a sensitive biomarker of aging. This study investigated if phosphorylation of H2A.X in peripheral blood mononuclear cells (PBMCs) is associated with cardiometabolic risk in nondiabetic individuals. Basic parameters and oxidative stress/inflammatory markers were measured in nondiabetic healthy Koreans (n = 119). Phosphorylation of H2A.X was measured randomly among the study subjects using a flow cytometer. According to the number of metabolic syndrome risk factor (MetS-RF), the study subjects were subdivided into "super healthy" (MetS - RF = 0, n = 71) and "MetS-risk" (MetS - RF ? 1, n = 48) groups. Phosphorylation of H2A.X in PBMCs (percentages and mean fluorescence intensity) was significantly higher in the MetS-risk group than in the super healthy group after adjusting for age, sex, cigarette smoking, and alcohol consumption. Phosphorylated H2A.X was positively correlated with the number of MetS-RF as well as waist circumference, blood pressures, triglyceride, HbA1C, oxidized LDL, high sensitivity C-reactive protein, tumor necrosis factor-alpha, and alanine aminotransferase after the adjustment. The present study suggested that phosphorylated H2A.X in circulating PBMCs measured by flow cytometer may be a useful marker for monitoring cardiometabolic risk in nondiabetic individuals.

SUBMITTER: Yoon SR

PROVIDER: S-EPMC5441116 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Phosphorylation of Histone H2A.X in Peripheral Blood Mononuclear Cells May Be a Useful Marker for Monitoring Cardiometabolic Risk in Nondiabetic Individuals.

Yoon So Ra SR Song Juhyun J Lee Jong Hwa JH Kim Oh Yoen OY

Disease markers 20170509

Phosphorylation of H2A.X (serine 139) in the histone H2A family located in the downstream of the DNA damage kinase signaling cascade is an important indicator of DNA damage. Recently, phosphorylation of H2A.X was proposed as a sensitive biomarker of aging. This study investigated if phosphorylation of H2A.X in peripheral blood mononuclear cells (PBMCs) is associated with cardiometabolic risk in nondiabetic individuals. Basic parameters and oxidative stress/inflammatory markers were measured in n ...[more]

PMID: 28572698

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Project description:BackgroundMultiple sclerosis (MS) is characterized by increased activation of peripheral blood mononuclear cells (PBMCs), linked to perturbations in the phosphorylation of signaling proteins.MethodsWe developed a phosphoflow cytometry protocol to assess the levels of 11 phosphorylated nuclear proteins at baseline conditions and after cell activation in distinct PBMC populations from 41 treatment-naïve relapsing-remitting (RR) MS subjects and 37 healthy controls, and in a second cohort of 9 untreated RRMS patients and 10 secondary progressive (SP) MS patients. Levels of HLA-ABC, HLA-E, and HLA-DR were also assessed. Phosphorylation levels of selected proteins were also assessed in mouse splenocytes isolated from myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE).ResultsModest differences were observed at baseline between patients and controls, with general lower phosphorylation levels in cells from affected individuals. Conversely, a dramatic increase in phosphorylated p38MAPK and STAT proteins was observed across all cell types in MS patients compared to controls after in vitro activation. A similar phosphorylation profile was observed in mouse lymphocytes primed in vivo with MOG. Furthermore, levels of all p-STAT proteins were found directly correlated with HLA expression in monocytes. Levels of phosphorylated proteins did not differ between relapsing-remitting and secondary progressive MS patients either in baseline conditions or after stimulation. Lastly, phosphorylation levels appear to be independent of the genotype.ConclusionThe response to IFN-α through STAT proteins signaling is strongly dysregulated in MS patients irrespective of disease stage. These findings suggest that the aberrant activation of this pathway could lead to changes in the expression of HLA molecules in antigen presenting cells, which are known to play important roles in the regulation of the immune response in health and disease.

Dataset Information

Phosphorylation of Histone H2A.X in Peripheral Blood Mononuclear Cells May Be a Useful Marker for Monitoring Cardiometabolic Risk in Nondiabetic Individuals.

Publications

Phosphorylation of Histone H2A.X in Peripheral Blood Mononuclear Cells May Be a Useful Marker for Monitoring Cardiometabolic Risk in Nondiabetic Individuals.

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