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[细胞适应与钠钾ATP酶谷胱甘肽化相关的低氧含量的能力]

[The ability of cells to adjust to the low oxigen content associated with Na,K-ATPase glutationilation].

作者信息

Petrushanko I Iu, Simonenko O V, Burnysheva K M, Klimanova E A, Dergousova E A, Mit'kevich V A, Lopina O D, Makarov A A

出版信息

Mol Biol (Mosk). 2015 Jan-Feb;49(1):175-83.

Abstract

Decreasing the amount of oxygen in the tissues under hypoxic and ischemic conditions, observed at a number of pathologic processes, inevitably leads to their damage. One of the main causes of cell damage and death is a violation of the systems maintaining ionic balance. Na,K-ATPaseis a basic ion-transporting protein of animal cell plasma membrane and inhibition of the Na,K-ATPase activity at lower concentrations of oxygen is one of the earliest and most critical events for cell viability. Currently there is an active search for modulators of Na,K-ATPase activity. For this purpose traditionally used cardiac glycosides but the existence of serious adverse effects forced to look for alternative inhibitors of Na,K-ATPase. Previously we have found that the glutathionylation of Na,K-ATPase catalytic subunit leads to a complete-inhibition of the enzyme. In this paper it is shown that the agents which increase the level of Na,K-ATPase glutathionylation: ethyl glutathione (et-GSH), oxidized glutathione (GSSG) and N-acetyl cysteine (NAC), increase cell survival under oxygen deficiency conditions, prevent decline of ATP in the cells and normalize their redox status. Concentration range in which these substances have a maximum protective effect, and does not exhibit cytotoxic properties was defined: for et-GSH 0.2-0.5 mM, for GSSG 0.2-1 mM, for NAC 10 to 15 mM. The results show prospects for development of methods for tissues protection from damage caused by oxygen starvation by varying the degree of Na,K-ATPase glutathionylation.

摘要

在许多病理过程中观察到,在缺氧和缺血条件下组织中氧气量的减少不可避免地会导致组织损伤。细胞损伤和死亡的主要原因之一是维持离子平衡的系统遭到破坏。钠钾ATP酶是动物细胞质膜的一种基本离子转运蛋白,在较低氧浓度下抑制钠钾ATP酶的活性是影响细胞活力的最早且最关键的事件之一。目前人们正在积极寻找钠钾ATP酶活性的调节剂。传统上为此使用强心苷,但由于存在严重的不良反应,人们不得不寻找钠钾ATP酶的替代抑制剂。此前我们发现,钠钾ATP酶催化亚基的谷胱甘肽化会导致该酶完全被抑制。本文表明,能提高钠钾ATP酶谷胱甘肽化水平的试剂:乙基谷胱甘肽(et-GSH)、氧化型谷胱甘肽(GSSG)和N-乙酰半胱氨酸(NAC),可在缺氧条件下提高细胞存活率,防止细胞内ATP水平下降并使其氧化还原状态正常化。确定了这些物质具有最大保护作用且不表现出细胞毒性的浓度范围:et-GSH为0.2 - 0.5 mM,GSSG为0.2 - 1 mM,NAC为10至15 mM。结果显示了通过改变钠钾ATP酶谷胱甘肽化程度来开发保护组织免受缺氧损伤方法的前景。

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