Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species

Rationale: Angiotensin (Ang) II-induced 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. Objective:...

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Autores principales: Palomeque, Julieta, Velez Rueda, Omar, Sapia, Luciana, Valverde, Carlos Alfredo, Salas, Margarita Ana, Vila Petroff, Martín Gerardo, Mattiazzi, Alicia Ramona
Formato: Articulo
Lenguaje:Inglés
Publicado: 2009
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/82711
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id I19-R120-10915-82711
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Angiotensin II
Apoptosis
CaMKII
Reactive oxygen species
spellingShingle Ciencias Médicas
Angiotensin II
Apoptosis
CaMKII
Reactive oxygen species
Palomeque, Julieta
Velez Rueda, Omar
Sapia, Luciana
Valverde, Carlos Alfredo
Salas, Margarita Ana
Vila Petroff, Martín Gerardo
Mattiazzi, Alicia Ramona
Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species
topic_facet Ciencias Médicas
Angiotensin II
Apoptosis
CaMKII
Reactive oxygen species
description Rationale: Angiotensin (Ang) II-induced 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. Objective: 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-induced apoptosis. Methods and results: Ang II (1 μmol/L) reduced cat/rat myocytes viability by ≈40%, in part, because of apoptosis (TUNEL/caspase-3 activity). In both species, apoptosis was associated with reactive oxygen species (ROS) production, Ca2+/calmodulin-dependent 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-induced cell mortality. Moreover, although KN-93 did not affect Ang II-induced ROS production, it prevented p38MAPK activation. Results further show that CaMKII can be activated by Ang II or H2O2, even in the presence of the Ca 2+chelator BAPTA-AM, in myocytes and in EGTA-Ca2-free solutions in the presence of the calmodulin inhibitor W-7 in in vitro experiments. Conclusions: (1) The Ang II-induced 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 Ca2+concentrations, suggesting a new mechanism by which ROS reset the Ca2+dependence of CaMKII to extremely low Ca2+levels.
format Articulo
Articulo
author Palomeque, Julieta
Velez Rueda, Omar
Sapia, Luciana
Valverde, Carlos Alfredo
Salas, Margarita Ana
Vila Petroff, Martín Gerardo
Mattiazzi, Alicia Ramona
author_facet Palomeque, Julieta
Velez Rueda, Omar
Sapia, Luciana
Valverde, Carlos Alfredo
Salas, Margarita Ana
Vila Petroff, Martín Gerardo
Mattiazzi, Alicia Ramona
author_sort Palomeque, Julieta
title Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species
title_short Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species
title_full Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species
title_fullStr Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species
title_full_unstemmed Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species
title_sort angiotensin ii-induced oxidative stress resets the ca2+ dependence of ca2+-calmodulin protein kinase ii and promotes a death pathway conserved across different species
publishDate 2009
url http://sedici.unlp.edu.ar/handle/10915/82711
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