Study of Na+/K+-ATPase and Components of the Ca2+-Transporting System in Myocardium under Experimental Prediabetes and Type 1 Diabetes in Rats

IF 0.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
I. B. Sukhov, O. V. Chistyakova, M. G. Dobretsov
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引用次数: 0

Abstract

One of the complications of diabetes mellitus (DM) is diabetic cardiomyopathy (DCM), whose molecular mechanisms of pathogenesis have not been fully studied. Previously, the involvement of Na+/K+-ATPase and components of the Ca2+ transport system in cardiomyocytes in the development of DCM was shown. The aim of the work was to study the expression and activity of Na+/K+-ATPase and Ca2+-ATPase (SERCA2) in the myocardium of male Wistar rats in a model of streptozotocin (STZ)-induced prediabetes and overt type 1 diabetes (T1DM). STZ was administered at once i.p. in doses of 30–35 mg/kg. Rats with glucose levels above 11 mM were considered diabetic (STZ-D1 group), and those with moderate hyperglycemia were considered prediabetic (STZ-preD1 group). The activity of Na+/K+-ATPase and Ca2+-ATPase was determined (by the rate of release of inorganic phosphate, Pi), and the expression of the genes α1- and α2-isoforms of Na+/K+-ATPase, SERCA2, and Kir6.1, Kv7.1, and Kv2.1 potassium channels was also determined. In the control (C) group, the activity of ouabain (1 mM) -sensitive Mg2+-dependent ATPase was 6.03 ± 0.6 mmol Pi/g/h. In the STZ-D1 and STZ-preD1 groups, Na+/K+-ATPase activity did not differ from group C. The level of gene expression of α1- and α2- subunits of Na+/K+-ATPase in the STZ-D1 group decreased by more than 45%, then both in the STZ-preD1 group increased by 64 and 81%, which may indicate a high sensitivity of expression to insulinopenia. The activity of Ca2+-ATPase and the expression of the SERCA2 gene did not differ between the groups, which might be because the 4-week period after STZ administration is not sufficient for the development of Ca2+-ATPase deficiency in the rat heart. The level of expression of the genes of the potassium channel subtypes Kv2.1, Kir6.1, and Kv7.1 increased in the STZ-preD1 group, which may indicate a potential contribution of the studied potassium channel subtypes to the adaptation mechanism to moderate hyperglycemia.

Abstract Image

实验性糖尿病前期和 1 型糖尿病大鼠心肌中 Na+/K+-ATP 酶和 Ca2+ 转运系统成分的研究
摘要 糖尿病(DM)的并发症之一是糖尿病心肌病(DCM),其发病的分子机制尚未得到充分研究。以前的研究表明,心肌细胞中的 Na+/K+-ATPase 和 Ca2+ 转运系统的组分参与了 DCM 的发病。这项工作的目的是研究在链脲佐菌素(STZ)诱导的糖尿病前期和明显的 1 型糖尿病(T1DM)模型中,雄性 Wistar 大鼠心肌中 Na+/K+-ATP 酶和 Ca2+-ATP 酶(SERCA2)的表达和活性。STZ 以 30-35 毫克/千克的剂量一次性静脉注射。血糖水平超过 11 mM 的大鼠被视为糖尿病大鼠(STZ-D1 组),中度高血糖大鼠被视为糖尿病前期大鼠(STZ-PreD1 组)。测定了 Na+/K+-ATPase 和 Ca2+-ATPase 的活性(通过无机磷酸盐 Pi 的释放速度),还测定了 Na+/K+-ATPase α1-和 α2-异构体、SERCA2 和 Kir6.1、Kv7.1 和 Kv2.1 钾通道基因的表达。在对照(C)组中,对乌苯那敏(1 mM)敏感的 Mg2+ 依赖性 ATPase 的活性为 6.03 ± 0.6 mmol Pi/g/h。STZ-D1组和STZ-preD1组的Na+/K+-ATPase活性与C组没有差异。Na+/K+-ATPase的α1-亚基和α2-亚基的基因表达水平在STZ-D1组下降了45%以上,而在STZ-preD1组则分别增加了64%和81%,这可能表明基因表达对胰岛素分泌减少具有高度敏感性。Ca2+-ATPase的活性和SERCA2基因的表达在各组间没有差异,这可能是因为STZ给药后4周的时间不足以使大鼠心脏发生Ca2+-ATPase缺乏症。钾通道亚型 Kv2.1、Kir6.1 和 Kv7.1 基因的表达水平在 STZ-preD1 组有所增加,这可能表明所研究的钾通道亚型对高血糖的适应机制有潜在的贡献。
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来源期刊
自引率
33.30%
发文量
110
审稿时长
6-12 weeks
期刊介绍: Journal of Evolutionary Biochemistry and Physiology  publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.
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