{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:30:03Z","timestamp":1789194603790,"version":"build-2803163510"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,12,4]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Rationale:<\/jats:italic>\n            <\/jats:bold>\n            Angiotensin (Ang) II\u2013induced apoptosis was reported to be mediated by different signaling molecules. Whether these molecules are either interconnected in a single pathway or constitute different and alternative cascades by which Ang II exerts its apoptotic action, is not known.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Objective:<\/jats:italic>\n            <\/jats:bold>\n            To investigate in cultured myocytes from adult cat and rat, 2 species in which Ang II has opposite inotropic effects, the signaling cascade involved in Ang II\u2013induced apoptosis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results:<\/jats:italic>\n            <\/jats:bold>\n            Ang II (1 \u03bcmol\/L) reduced cat\/rat myocytes viability by \u224840%, in part, because of apoptosis (TUNEL\/caspase-3 activity). In both species, apoptosis was associated with reactive oxygen species (ROS) production, Ca\n            <jats:sup>2+<\/jats:sup>\n            \/calmodulin\u2013dependent protein kinase (CaMK)II, and p38 mitogen-activated protein kinase (p38MAPK) activation and was prevented by the ROS scavenger MPG (2-mercaptopropionylglycine) or the NADPH oxidase inhibitor DPI (diphenyleneiodonium) by CaMKII inhibitors (KN-93 and AIP [autocamtide 2-related inhibitory peptide]) or in transgenic mice expressing a CaMKII inhibitory peptide and by the p38MAPK inhibitor, SB202190. Furthermore, p38MAPK overexpression exacerbated Ang II\u2013induced cell mortality. Moreover, although KN-93 did not affect Ang II\u2013induced ROS production, it prevented p38MAPK activation. Results further show that CaMKII can be activated by Ang II or H\n            <jats:sub>2<\/jats:sub>\n            O\n            <jats:sub>2<\/jats:sub>\n            , even in the presence of the Ca\n            <jats:sup>2+<\/jats:sup>\n            chelator BAPTA-AM, in myocytes and in EGTA-Ca\n            <jats:sup>2+<\/jats:sup>\n            \u2013free solutions in the presence of the calmodulin inhibitor W-7 in in vitro experiments.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions:<\/jats:italic>\n            <\/jats:bold>\n            (1) The Ang II\u2013induced apoptotic cascade converges in both species, in a common pathway mediated by ROS-dependent CaMKII activation which results in p38MAPK activation and apoptosis. (2) In the presence of Ang II or ROS, CaMKII may be activated at subdiastolic Ca\n            <jats:sup>2+<\/jats:sup>\n            concentrations, suggesting a new mechanism by which ROS reset the Ca\n            <jats:sup>2+<\/jats:sup>\n            dependence of CaMKII to extremely low Ca\n            <jats:sup>2+<\/jats:sup>\n            levels.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.204172","type":"journal-article","created":{"date-parts":[[2009,10,23]],"date-time":"2009-10-23T02:16:20Z","timestamp":1256264180000},"page":"1204-1212","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":138,"title":["Angiotensin II\u2013Induced Oxidative Stress Resets the Ca\n            <sup>2+<\/sup>\n            Dependence of Ca\n            <sup>2+<\/sup>\n            \u2013Calmodulin Protein Kinase II and Promotes a Death Pathway Conserved Across Different Species"],"prefix":"10.1161","volume":"105","author":[{"given":"Julieta","family":"Palomeque","sequence":"first","affiliation":[{"name":"From the Centro de Investigaciones Cardiovasculares, Facultad Medicina, Universidad Nacional de La Plata, Centro Cienti\u0301fico Tecnolo\u0301gico CONICET La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar Velez","family":"Rueda","sequence":"additional","affiliation":[{"name":"From the Centro de Investigaciones Cardiovasculares, Facultad Medicina, Universidad Nacional de La Plata, Centro Cienti\u0301fico Tecnolo\u0301gico CONICET La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Sapia","sequence":"additional","affiliation":[{"name":"From the Centro de Investigaciones Cardiovasculares, Facultad Medicina, Universidad Nacional de La Plata, Centro Cienti\u0301fico Tecnolo\u0301gico CONICET La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Valverde","sequence":"additional","affiliation":[{"name":"From the Centro de Investigaciones Cardiovasculares, Facultad Medicina, Universidad Nacional de La Plata, Centro Cienti\u0301fico Tecnolo\u0301gico CONICET La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Salas","sequence":"additional","affiliation":[{"name":"From the Centro de Investigaciones Cardiovasculares, Facultad Medicina, Universidad Nacional de La Plata, Centro Cienti\u0301fico Tecnolo\u0301gico CONICET La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Vila","family":"Petroff","sequence":"additional","affiliation":[{"name":"From the Centro de Investigaciones Cardiovasculares, Facultad Medicina, Universidad Nacional de La Plata, Centro Cienti\u0301fico Tecnolo\u0301gico CONICET La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Mattiazzi","sequence":"additional","affiliation":[{"name":"From the Centro de Investigaciones Cardiovasculares, Facultad Medicina, Universidad Nacional de La Plata, Centro Cienti\u0301fico Tecnolo\u0301gico CONICET La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.87.12.1180"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1996.0333"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01301.2007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-5299.2002.00717.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e318181fadd"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611507200"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.12.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.048"},{"key":"e_1_3_3_9_2","first-page":"764.","volume":"44","year":"2008","unstructured":"Palomeque J, Valverde CA, Velez Rueda JO, Salas MA, Mattiazzi A, Vila Petroff M. 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