In dialyzed squid axons oxidative stress inhibits the Na+/Ca2+ exchanger by impairing the Cai2+-regulatory site
In dialyzed squid axons oxidative stress inhibits the Na+/Ca2+ exchanger by impairing the Cai2+-regulatory site
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DOI：
10.1152/ajpcell.00521.2010
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发表时间：
2011-09-01
影响因子：
5.5
通讯作者：
Beauge, Luis
中科院分区：
文献类型：
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作者：
DiPolo, Reinaldo;Beauge, Luis
Dipolo R，Beauge L.在透析的鱿鱼轴突中，氧化应激通过损害Ca-i(2+)调节位点来抑制Na+/Ca2+交换。Am J Physiol Cell Physiol 301：C687-C694,2011。2011年6月1日首次出版；DOI：10.1152/ajpcell.00521.2010-Na+/Ca~(2+)交换，细胞排出钙的主要机制，参与多种生理和生理病理相互作用。在这项工作中，我们使用透析的鱿鱼巨大轴突来研究两种氧化剂，SIN-1缓冲的过氧亚硝酸盐和过氧化氢(H_2O_2)在没有和存在MgATP上调的情况下对Na+/Ca~(2+)交换的影响。结果表明，过氧亚硝酸根和过氧化氢诱导的氧化应激通过损伤细胞内钙离子(Ca-i(2+))调节部位而抑制Na+/Ca~(2+)交换，而不损害细胞内Na~+和Ca~(2+)转运部位。这种作用可以被镁三磷酸腺苷的存在和细胞内的碱化有效地抵消，这些条件也保护了H-I(+)和(H-I(+)+Na-I(+))对Ca-I(2+)调节位点的抑制。此外，1 mM的胞内EGTA可减少氧化抑制。然而，一旦安装了氧化剂的影响，它们就不能被镁-三磷酸腺苷或EGTA逆转。这些结果对于Na+/Ca~(2+)交换在导致组织缺血-再灌注和缺氧/复氧的病理条件反应中的作用具有重要意义；它们与ATP浓度显著降低、氧化剂产生增加和细胞内Ca~(2+)浓度升高一致，这似乎是导致细胞损伤的主要因素。
DiPolo R, Beauge L. In dialyzed squid axons oxidative stress inhibits the Na+/Ca2+ exchanger by impairing the Ca-i(2+)-regulatory site. Am J Physiol Cell Physiol 301: C687-C694, 2011. First published June 1, 2011; doi: 10.1152/ajpcell.00521.2010.-The Na+/Ca2+ exchanger, a major mechanism by which cells extrude calcium, is involved in several physiological and physiopathological interactions. In this work we have used the dialyzed squid giant axon to study the effects of two oxidants, SIN-1-buffered peroxynitrite and hydrogen peroxide (H2O2), on the Na+/Ca2+ exchanger in the absence and presence of MgATP upregulation. The results show that oxidative stress induced by peroxynitrite and hydrogen peroxide inhibits the Na+/Ca2+ exchanger by impairing the intracellular Ca2+ (Ca-i(2+))regulatory sites, leaving unharmed the intracellular Na+- and Ca2+-transporting sites. This effect is efficiently counteracted by the presence of MgATP and by intracellular alkalinization, conditions that also protect H-i(+) and (H-i(+) + Na-i(+)) inhibition of Ca-i(2+)-regulatory sites. In addition, 1 mM intracellular EGTA reduces oxidant inhibition. However, once the effects of oxidants are installed they cannot be reversed by either MgATP or EGTA. These results have significant implications regarding the role of the Na+/Ca2+ exchanger in response to pathological conditions leading to tissue ischemia-reperfusion and anoxia/reoxygenation; they concur with a marked reduction in ATP concentration, an increase in oxidant production, and a rise in intracellular Ca2+ concentration that seems to be the main factor responsible for cell damage.