| http://purl.uniprot.org/citations/18845810 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18845810 | http://www.w3.org/2000/01/rdf-schema#comment | "Heme oxygenase (HO)-1 is a protective antioxidant enzyme that prevents cardiomyocyte apoptosis, for instance, during progressive cardiomyopathy. Here we identify a fundamental aspect of the HO-1 protection mechanism by demonstrating that HO-1 activity in mouse heart stimulates the bigenomic mitochondrial biogenesis program via induction of NF-E2-related factor (Nrf)2 gene expression and nuclear translocation. Nrf2 upregulates the mRNA, protein, and activity for HO-1 as well as mRNA and protein for nuclear respiratory factor (NRF)-1. Mechanistically, in cardiomyocytes, endogenous carbon monoxide (CO) generated by HO-1 overexpression stimulates superoxide dismutase-2 upregulation and mitochondrial H(2)O(2) production, which activates Akt/PKB. Akt deactivates glycogen synthase kinase-3beta, which permits Nrf2 nuclear translocation and occupancy of 4 antioxidant response elements (AREs) in the NRF-1 promoter. The ensuing accumulation of nuclear NRF-1 protein leads to gene activation for mitochondrial biogenesis, which opposes apoptosis and necrosis caused by the cardio-toxic anthracycline chemotherapeutic agent, doxorubicin. In cardiac cells, Akt silencing exacerbates doxorubicin-induced apoptosis, and in vivo CO rescues wild-type but not Akt1(-/-) mice from doxorubicin cardiomyopathy. These findings consign HO-1/CO signaling through Nrf2 and Akt to the myocardial transcriptional program for mitochondrial biogenesis, provide a rationale for targeted mitochondrial CO therapy, and connect cardiac mitochondrial volume expansion with the inducible network of xenobiotic and antioxidant cellular defenses."xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.org/dc/terms/identifier | "doi:10.1161/01.res.0000338597.71702.ad"xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/author | "Babiker A."xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/author | "Piantadosi C.A."xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/author | "Suliman H.B."xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/author | "Carraway M.S."xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/name | "Circ Res"xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/pages | "1232-1240"xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/title | "Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1."xsd:string |
| http://purl.uniprot.org/citations/18845810 | http://purl.uniprot.org/core/volume | "103"xsd:string |
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