Loss of PKC-delta alters cardiac metabolism.
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).
Mayr
Manuel
M
Department of Cardiac and Vascular Sciences, St George's Hospital Medical School, London SW17 0RE, UK.
Chung
Yuen-Li
YL
Mayr
Ursula
U
McGregor
Emma
E
Troy
Helen
H
Baier
Gottfried
G
Leitges
Michael
M
Dunn
Michael J
MJ
Griffiths
John R
JR
Xu
Qingbo
Q
D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism; D054464:Peroxiredoxins; D011493:Protein Kinase C / Q000172:deficiency / Q000502:physiology*; D051745:Protein Kinase C-delta; D020543:Proteome / Q000378:metabolism
D018832:Molecular Chaperones; D020543:Proteome; D010544:Peroxidases; D054464:Peroxiredoxins; C497259:Prkcd protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta