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dc.creatorToledo, Flavia Daniela-
dc.creatorPerez, Leonardo Martin-
dc.creatorBasiglio, Cecilia Lorena-
dc.creatorOchoa, Justina Elena-
dc.creatorSanchez Pozzi, Enrique Juan-
dc.creatorRoma, Marcelo Gabriel-
dc.date2016-06-08T14:01:48Z-
dc.date2016-06-08T14:01:48Z-
dc.date2014-03-
dc.date2016-06-01T14:01:32Z-
dc.date.accessioned2019-04-29T15:34:49Z-
dc.date.available2019-04-29T15:34:49Z-
dc.date.issued2014-03-
dc.identifierToledo, Flavia Daniela; Perez, Leonardo Martin; Basiglio, Cecilia Lorena; Ochoa, Justina Elena; Sanchez Pozzi, Enrique Juan; et al.; The Ca2+-calmodulin-Ca2+/calmodulin- dependent protein kinase II signaling pathway is involved in oxidative stress-induced mitochondrial permeability transition and apoptosis in isolated rat hepatocytes; Springer; Archives of Toxicology; 88; 9; 3-2014; 1695-1709-
dc.identifier0340-5761-
dc.identifierhttp://hdl.handle.net/11336/6104-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/297051-
dc.descriptionOxidative stress (OS) is a common event in most hepatopathies, leading to mitochondrial permeability transition pore (MPTP) formation and further exacerbation of both OS from mitochondrial origin and cell death. Intracellular Ca2+ increase plays a permissive role in these events, but the underlying mechanisms are poorly known. We examined in primary cultured rat hepatocytes whether the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) signaling pathway is involved in this process, by using tert-butyl hydroperoxide (tBOOH) as a pro-oxidant, model compound. tBOOH (500 μM, 15 min) induced MPTP formation, as assessed by measuring mitochondrial membrane depolarization as a surrogate marker, and increased lipid peroxidation in a cyclosporin A (CsA)-sensitive manner, revealing the involvement of MPTPs in tBOOH-induced radical oxygen species (ROS) formation. Intracellular Ca2+ sequestration with BAPTA/AM, CaM blockage with W7 or trifluoperazine, and CaMKII inhibition with KN-62 all fully prevented tBOOH-induced MPTP opening and reduced tBOOH-induced lipid peroxidation to a similar extent to CsA, suggesting that Ca2+/CaM/CaMKII signaling pathway fully mediates MPTP-mediated mitochondrial ROS generation. tBOOH-induced apoptosis, as shown by flow cytometry of annexin V/propidium iodide, mitochondrial release of cytochrome c, activation of caspase-3 and increase in the Bax-to-Bcl-xL ratio, and the Ca2+/CaM/CaMKII signaling antagonists fully prevented these effects. Intramitochondrial CaM and CaMKII were partially involved in tBOOH-induced MPTP formation, since W7 and KN-62 both attenuated the tBOOH-induced, MPTP-mediated swelling of isolated mitochondria. We concluded that Ca2+/CaM/CaMKII signaling pathway is a key mediator of OS-induced MPTP formation and the subsequent exacerbation of OS from mitochondrial origin and apoptotic cell death.-
dc.descriptionFil: Toledo, Flavia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina-
dc.descriptionFil: Perez, Leonardo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina-
dc.descriptionFil: Basiglio, Cecilia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina-
dc.descriptionFil: Ochoa, Justina Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina-
dc.descriptionFil: Sanchez Pozzi, Enrique Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina-
dc.descriptionFil: Roma, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina-
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dc.languageeng-
dc.publisherSpringer-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs00204-014-1219-5-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00204-014-1219-5-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00204-014-1219-5-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectOXIDATIVE STRESS-
dc.subjectTERT-BUTYL HYDROPEROXIDE-
dc.subjectCa2+/CALMODULIN-DEPENDENT PROTEIN KINASE II-
dc.subjectMITOCHONDRIAL PERMEABILITY TRANSITION PORE-
dc.subjectAPOPTOSIS-
dc.subjectCYTOCHROME C-
dc.subjectBioquímica y Biología Molecular-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleThe Ca2+-calmodulin-Ca2+/calmodulin- dependent protein kinase II signaling pathway is involved in oxidative stress-induced mitochondrial permeability transition and apoptosis in isolated rat hepatocytes-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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