| First Author | Mascareno E | Year | 2009 |
| Journal | J Cell Mol Med | Volume | 13 |
| Issue | 8B | Pages | 2744-53 |
| PubMed ID | 18624753 | Mgi Jnum | J:156227 |
| Mgi Id | MGI:4419075 | Doi | 10.1111/j.1582-4934.2008.00404.x |
| Citation | Mascareno E, et al. (2008) Down-regulation of cardiac lineage protein (CLP-1) expression in CLP-1 +/- mice affords cardioprotection against ischaemic stress. J Cell Mol Med |
| abstractText | In order to understand the transcriptional mechanism that underlies cell protection to stress, we evaluated the role of CLP-1, a known inhibitor of the transcription elongation complex (pTEFb), in CLP-1 +/- mice hearts. Using the isolated heart model, we observed that the CLP-1+/- hearts, when subjected to ischemic stress and evaluated by hemodynamic measurements, exhibit significant cardioprotection. CLP-1 remains associated with the pTEFb complex in the heterozygous hearts, where as it is released in the wild type hearts suggesting the involvement of pTEFb regulation in cell protection. There was a decrease in Cdk7 and Cdk9 kinase activity and consequently in phosphorylation of serine-5 and serine-2 of Pol II CTD in CLP-1 +/- hearts. However, the levels of mitochondrial proteins, PGC-1alpha and HIF-1alpha, which enhance mitochondrial activity and are implicated in cell survival, were increased in CLP-1+/- hearts subjected to ischemic stress compared to that in wild-type CLP-1+/+ hearts treated identically. There was also an increase in expression of pyruvate dehydrogenase kinase (PDK-1) which facilitates cell adaptation to hypoxic stress. Taken together, our data suggest that regulation of the CLP-1 levels is critical to cellular adaptation of the survival program that protects cardiomyocytes against stress due collectively to a decrease in RNA Pol II phosphorylation but an increase in expression of target proteins that regulate mitochondrial function and metabolic adaptation to stress. |
