North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia; Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia.
North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia; Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia.
Free Radic Biol Med. 2012 Dec 15;53(12):2263-8. doi: 10.1016/j.freeradbiomed.2012.10.539. Epub 2012 Oct 17.
The Na(+)-K(+) pump is an essential heterodimeric membrane protein, which maintains electrochemical gradients for Na(+) and K(+) across cell membranes in all tissues. We have identified glutathionylation, a reversible posttranslational redox modification, of the Na(+)-K(+) pump's β1 subunit as a regulatory mechanism of pump activity. Oxidative inhibition of the Na(+)-K(+) pump by angiotensin II- and β1-adrenergic receptor-coupled signaling via NADPH oxidase activation demonstrates the relevance of this regulatory mechanism in cardiovascular physiology and pathophysiology. This has implications for dysregulation of intracellular Na(+) and Ca(2+) as well as increased oxidative stress in heart failure, myocardial ischemia-reperfusion, and regulation of vascular tone under conditions of elevated oxidative stress. Treatment strategies that are able to reverse this oxidative inhibition of the Na(+)-K(+) pump have the potential for cardiovascular-protective effects.
钠钾泵是一种重要的异二聚体膜蛋白，它维持着所有组织细胞膜内外钠离子和钾离子的电化学梯度。我们已经发现，钠钾泵β1 亚基的谷胱甘肽化是一种可逆的翻译后氧化还原修饰，是泵活性的调节机制。血管紧张素 II 和β1 肾上腺素能受体偶联信号通过 NADPH 氧化酶激活对钠钾泵的氧化抑制，证明了这种调节机制在心血管生理学和病理生理学中的相关性。这对心力衰竭、心肌缺血再灌注以及氧化应激升高条件下血管张力的调节中细胞内钠离子和钙离子的失调以及氧化应激增加有影响。能够逆转钠钾泵这种氧化抑制的治疗策略有可能具有心血管保护作用。
