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Herein, we addressed the temporal responses in coupled Ca<jats:sup>2+<\/jats:sup>and Zn<jats:sup>2+<\/jats:sup>dyshomeostasis, reflecting the prooxidant-antioxidant equilibrium, by examining preclinical ( week 1) and pathological ( week 4) stages of ALDOST to determine whether endogenous antioxidant defenses would be ultimately overwhelmed to account for this delay in cardiac remodeling. We compared responses in cardiomyocyte free [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and [Zn<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and mitochondrial total [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>m<\/jats:sub>and [Zn<jats:sup>2+<\/jats:sup>]<jats:sub>m<\/jats:sub>, together with biomarkers of oxidative stress and antioxidant defenses, during 1- and 4-wk ALDOST. At week 1 and compared with controls, we found: 1) elevations in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>m<\/jats:sub>were coupled with [Zn<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and [Zn<jats:sup>2+<\/jats:sup>]<jats:sub>m<\/jats:sub>; 2) increased mitochondrial H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>production, cardiomyocyte xanthine oxidase activity, and cardiac and mitochondrial 8-isoprostane levels, counterbalanced by increased activity of antioxidant proteins, enzymes, and the nonenzymatic antioxidants that can be considered as cumulative antioxidant capacity; some of these enzymes and proteins (e.g., metallothionein-1, Cu\/Zn-superoxide, glutathione synthase) are regulated by metal-responsive transcription factor-1; and 3) although these augmented antioxidant defenses were sustained at week 4, they fell short in combating the persistent intracellular Ca<jats:sup>2+<\/jats:sup>overloading and marked rise in cardiac tissue 8-isoprostane and mitochondrial transition pore opening. Thus a coupled Ca<jats:sup>2+<\/jats:sup>and Zn<jats:sup>2+<\/jats:sup>dyshomeostasis occurs early during ALDOST in cardiac myocytes and mitochondria that regulate redox equilibrium until week 4 when ongoing intracellular Ca<jats:sup>2+<\/jats:sup>overloading and prooxidants overwhelm antioxidant defenses.<\/jats:p>","DOI":"10.1152\/ajpheart.00593.2009","type":"journal-article","created":{"date-parts":[[2009,11,14]],"date-time":"2009-11-14T03:15:15Z","timestamp":1258168515000},"page":"H385-H394","source":"Crossref","is-referenced-by-count":37,"title":["Temporal responses to intrinsically coupled calcium and zinc dyshomeostasis in cardiac myocytes and mitochondria during aldosteronism"],"prefix":"10.1152","volume":"298","author":[{"given":"German","family":"Kamalov","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Ahokas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atta U.","family":"Shahbaz","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal K.","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan C.","family":"Gerling","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, University of Tennessee Health Science Center, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl T.","family":"Weber","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-3718com"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000151516.84238.37"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000081980.63146.69"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e318167b0bd"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00301-9"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature03434"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000069215.36389.8D"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.89.1.151"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.65.3.657"},{"key":"B10","unstructured":"Bhattacharya SK, Crawford AJ, Thakar JH, Johnson PL. 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