Oxydative stress in type 2 diabetic patients: involvement of HIF-1 alpha AND mTOR genes expression

Y. Saenko, O. Gonchar, I. Mankovska, T. Drevytska, L. V. Bratus, B. Mankovsky
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Abstract

Biochemical and genetic mechanisms of oxidative stress (OS) developing in blood of patients with type 2 Diabetes mellitus (T2DM) were studied. Twenty patients with T2DM and 10 healthy persons participated in this study. Lipid peroxidation, the content of protein carbonyls and H2O2 production were measured in blood plasma and erythrocytes as OS biomarkers. Activity of SOD, catalase, and GPx as well as reduced glutathionе (GSH) level in plasma and erythrocytes were estimated. The gene expression of key regulators of oxygen and metabolic homeostasis (HIF-1α and mTOR) in leukocytes was studied. It was found a significant rise of TBARS and protein carbonyls content in plasma as well as of H2O2 production in erythrocytes from patients with T2DM compared to control. The diabetic patients also demonstrated an increase in the SOD and catalase activity in plasma and significantly lower GSH content and GPx activity in erythrocytes compared to the healthy participants. The established marked inhibition of mTOR gene expression and the tendency to an increase in HIF-1α gene expression in leukocytes of patients with T2DM may serve as a protective mechanism which counteracts OS developing and oxidative cell damage. Keywords: HIF-1α, mTOR, oxidative stress, type 2 diabetes mellitus
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2型糖尿病患者的氧化应激:HIF-1 α和mTOR基因表达的参与
研究了2型糖尿病(T2DM)患者血液中氧化应激(OS)发生的生化和遗传机制。2型糖尿病患者20例,健康人10例。血浆和红细胞中脂质过氧化、蛋白羰基含量和H2O2生成作为OS的生物标志物。测定血浆和红细胞中SOD、过氧化氢酶、GPx活性及还原型谷胱甘肽(GSH)水平。研究了白细胞中氧代谢稳态关键调控因子HIF-1α和mTOR的基因表达。结果发现,与对照组相比,T2DM患者血浆中TBARS和蛋白羰基含量以及红细胞中H2O2生成显著升高。与健康参与者相比,糖尿病患者血浆中SOD和过氧化氢酶活性升高,红细胞中GSH含量和GPx活性显著降低。T2DM患者白细胞中mTOR基因表达的明显抑制和HIF-1α基因表达的增加趋势可能是一种对抗OS发生和氧化细胞损伤的保护机制。关键词:HIF-1α, mTOR,氧化应激,2型糖尿病
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