| First Author | Mayr M | Year | 2004 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 287 |
| Issue | 2 | Pages | H937-45 |
| PubMed ID | 15277208 | Mgi Jnum | J:95584 |
| Mgi Id | MGI:3526599 | Doi | 10.1152/ajpheart.00877.2003 |
| Citation | Mayr M, et al. (2004) Loss of PKC-delta alters cardiac metabolism. Am J Physiol Heart Circ Physiol 287(2):H937-45 |
| abstractText | PKC-delta is believed to play an essential role in cardiomyocyte growth. In the present study, we investigated the effect of PKC-delta on cardiac metabolism using PKC-delta knockout mice generated in our laboratories. Proteomic analysis of heart protein extracts revealed profound changes in enzymes related to energy metabolism: certain isoforms of glycolytic enzymes, e.g., lactate dehydrogenase and pyruvate kinase, were absent or decreased, whereas several enzymes involved in lipid metabolism, e.g., phosphorylated isoforms of acyl-CoA dehydrogenases, showed a marked increase in PKC-delta(-/-) hearts. Moreover, PKC-delta deficiency was associated with changes in antioxidants, namely, 1-Cys peroxiredoxin and selenium-binding protein 1, and posttranslational modifications of chaperones involved in cytoskeleton regulation, such as heat shock protein (HSP)20, HSP27, and the zeta-subunit of the cytosolic chaperone containing the T-complex polypeptide 1. High-resolution NMR analysis of cardiac metabolites confirmed a significant decrease in the ratio of glycolytic end products (alanine + lactate) to end products of lipid metabolism (acetate) in PKC-delta(-/-) hearts. Taken together, our data demonstrate that loss of PKC-delta causes a shift from glucose to lipid metabolism in murine hearts, and we provide a detailed description of the enzymatic changes on a proteomic level. The consequences of these metabolic alterations on sensitivity to myocardial ischemia are further explored in the accompanyingpaper (20). |
