{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T17:40:22Z","timestamp":1718646022568},"reference-count":50,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p> The Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> 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 (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>), on the Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger in the absence and presence of MgATP upregulation. The results show that oxidative stress induced by peroxynitrite and hydrogen peroxide inhibits the Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger by impairing the intracellular Ca<jats:sup>2+<\/jats:sup> (Ca<jats:sub>i<\/jats:sub><jats:sup>2+<\/jats:sup>)-regulatory sites, leaving unharmed the intracellular Na<jats:sup>+<\/jats:sup>\u2212 and Ca<jats:sup>2+<\/jats:sup>\u2212transporting sites. This effect is efficiently counteracted by the presence of MgATP and by intracellular alkalinization, conditions that also protect H<jats:sub>i<\/jats:sub><jats:sup>+<\/jats:sup> and (H<jats:sub>i<\/jats:sub><jats:sup>+<\/jats:sup> + Na<jats:sub>i<\/jats:sub><jats:sup>+<\/jats:sup>) inhibition of Ca<jats:sub>i<\/jats:sub><jats:sup>2+<\/jats:sup>-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<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> 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 Ca<jats:sup>2+<\/jats:sup> concentration that seems to be the main factor responsible for cell damage. <\/jats:p>","DOI":"10.1152\/ajpcell.00521.2010","type":"journal-article","created":{"date-parts":[[2011,6,3]],"date-time":"2011-06-03T09:51:38Z","timestamp":1307094698000},"page":"C687-C694","source":"Crossref","is-referenced-by-count":2,"title":["In dialyzed squid axons oxidative stress inhibits the Na<sup>+<\/sup>\/Ca<sup>2+<\/sup> exchanger by impairing the Ca<sub>i<\/sub><sup>2+<\/sup>-regulatory site"],"prefix":"10.1152","volume":"301","author":[{"given":"Reinaldo","family":"DiPolo","sequence":"first","affiliation":[{"name":"Marine Biological Laboratory, Woods Hole, Massachusetts;"},{"name":"Laboratorio de Fisiolog\u00eda Celular, Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas, Venezuela; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Beaug\u00e9","sequence":"additional","affiliation":[{"name":"Marine Biological Laboratory, Woods Hole, Massachusetts;"},{"name":"Laboratorio de Biof\u00edsica, Instituto M. y M. 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