Registro completo de metadatos
| Campo DC | Valor | Lengua/Idioma |
|---|---|---|
| dc.creator | Wan, Xianxiu | - |
| dc.creator | Gupta, Shivali | - |
| dc.creator | Zago, María Paola | - |
| dc.creator | Davidson, Mercy M. | - |
| dc.creator | Dousset, Pierre | - |
| dc.creator | Amoroso, Alejandro | - |
| dc.creator | Garg, Nisha Jain | - |
| dc.date | 2017-09-14T22:22:37Z | - |
| dc.date | 2017-09-14T22:22:37Z | - |
| dc.date | 2012-11-29 | - |
| dc.date | 2017-05-29T15:38:01Z | - |
| dc.date.accessioned | 2019-04-29T15:50:18Z | - |
| dc.date.available | 2019-04-29T15:50:18Z | - |
| dc.date.issued | 2012-11-29 | - |
| dc.identifier | Wan, Xianxiu; Gupta, Shivali; Zago, María Paola; Davidson, Mercy M.; Dousset, Pierre; et al.; Defects of mtDNA replication impaired mitochondrial biogenesis during Trypanosoma cruzi infection in human cardiomyocytes and Chagasic patients: The role of Nrf1/2 and antioxidant response; American Heart Association; Journal of the American Heart Association; 1; 6; 29-11-2012; 1-14 | - |
| dc.identifier | 2047-9980 | - |
| dc.identifier | http://hdl.handle.net/11336/24332 | - |
| dc.identifier | CONICET Digital | - |
| dc.identifier | CONICET | - |
| dc.identifier.uri | http://rodna.bn.gov.ar:8080/jspui/handle/bnmm/303359 | - |
| dc.description | Background Mitochondrial: dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1)–regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. Methods and Results: We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi–infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPARγ-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)–regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts. Conclusions: The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi–infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for replication and gene expression in Chagas disease. | - |
| dc.description | Fil: Wan, Xianxiu. University of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos | - |
| dc.description | Fil: Gupta, Shivali. University of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos | - |
| dc.description | Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina | - |
| dc.description | Fil: Davidson, Mercy M.. Columbia University; Estados Unidos | - |
| dc.description | Fil: Dousset, Pierre. Hospital San Bernardo; Argentina | - |
| dc.description | Fil: Amoroso, Alejandro. Hospital San Bernardo; Argentina | - |
| dc.description | Fil: Garg, Nisha Jain. University of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.language | eng | - |
| dc.publisher | American Heart Association | - |
| dc.relation | info:eu-repo/semantics/reference/url/http://jaha.ahajournals.org/content/1/6/e003855 | - |
| dc.relation | info:eu-repo/semantics/altIdentifier/url/http://jaha.ahajournals.org/content/1/6/e003855 | - |
| dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1161/JAHA.112.003855 | - |
| dc.rights | info:eu-repo/semantics/openAccess | - |
| dc.rights | https://creativecommons.org/licenses/by-nc/2.5/ar/ | - |
| dc.source | reponame:CONICET Digital (CONICET) | - |
| dc.source | instname:Consejo Nacional de Investigaciones Científicas y Técnicas | - |
| dc.source | instacron:CONICET | - |
| dc.subject | Chagas disease | - |
| dc.subject | Mitochondrial biogenesis | - |
| dc.subject | mtDNA replication | - |
| dc.subject | nNRF2 | - |
| dc.subject | Oxidative stress | - |
| dc.subject | PGC-1α | - |
| dc.subject | Trypanosoma cruzi | - |
| dc.subject | Bioquímica y Biología Molecular | - |
| dc.subject | Ciencias Biológicas | - |
| dc.subject | CIENCIAS NATURALES Y EXACTAS | - |
| dc.title | Defects of mtDNA replication impaired mitochondrial biogenesis during Trypanosoma cruzi infection in human cardiomyocytes and Chagasic patients: The role of Nrf1/2 and antioxidant response | - |
| dc.type | info:eu-repo/semantics/article | - |
| dc.type | info:eu-repo/semantics/publishedVersion | - |
| dc.type | info:ar-repo/semantics/articulo | - |
| Aparece en las colecciones: | CONICET | |
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