Abstract
ObjectiveTo determine the correlation between DNA methylation of p66Shc promoter and some markers of inflammatory and oxidative stress in chronic renal failure (CRF) patients compared with healthy subjects.MethodsAn observational cross-sectional study was conducted in the nephrology department at Sidi Bouzid Regional Hospital (Tunisia). In total, 39 patients with CRF and 37 healthy subjects were included. Several biochemical parameters were measured. Furthermore, markers of the oxidative and inflammatory status (MDA, TAS, SOD, and CRP) were evaluated. The p66Shc methylation status was determined using the methylation-specific PCR.ResultsOur results showed that levels of blood glucose, urea, creatinine, uric acid, ChT, TG, albuminuria, CRP and MDA were significantly elevated in CRF patients compared to controls. Furthermore, p66Shc promoter region was highly demethylated in CRF patients compared to healthy controls (84% vs 4%). Our data showed a positive correlation between p66Shc hypomethylation and levels of MDA (r = 0.93; p<0, 05) and CRP (r = 0.89; P <0, 05), as well as a significant negative correlation between p66Shc hypomethylation, TAS (r = -0.76; P <0, 05) and SOD (r = -0.77; p<0, 05) levels. Similarly, there was a positive correlation between p66Shc hypomethylation and the disease stages. Importantly, multiple regression analysis showed that p66shc DNA hypomethylation remains strongly correlated with MDA, CRP and stages of CRF.ConclusionThis study indicates that the DNA hypomethylation of p66shc promoter was correlated with oxidative and inflammatory stress and the disease stages in CRF patients.
Highlights
Chronic renal failure (CRF) represents a public health issue requiring cumbersome management due to its increasing incidence, its prevalence, its chronic nature and the economic cost of its management [1]
Regarding methylation of p66Shc promoter, our data (Fig 1) showed that CRF patients were characterized by an increased p66Shc hypomethylation (84%) as compared to controls (4%)
We found a significant increase in the prevalence of diabetes (31%) in patients with chronic renal failure compared with controls
Summary
Chronic renal failure (CRF) represents a public health issue requiring cumbersome management due to its increasing incidence, its prevalence, its chronic nature and the economic cost of its management [1]. Oxidative stress has been shown to activate several cell signaling pathways that have deleterious effects on the cell growth by inducing cell death via necrosis or apoptosis [14,15,16] Among these signaling pathways, that of Shc adaptor proteins family regulates different cellular functions [16]. Inhibition of p66Shc in p66Shc (-/-) double- mutant mice resulted in improved resistance to oxidative stress, longer life, and decreased ROS-induced apoptosis [16]. These literature reports certainly establish the role of p66shc in the genesis of oxidant stress. The main objective of the present study was to investigate the correlation between the DNA methylation level of p66Shc promoter and some markers of inflammatory and oxidative stress in CRF patients compared with healthy control subjects
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