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Document Version Version Comment Date Status
214444.0 [No comment] 15.07.2005 11:54 Released

ID: 214444.0, MPI für experimentelle Endokrinologie / Arbeitsgruppe Leitges
Loss of PKC-delta alters cardiac metabolism
Authors:Mayr, M.; Chung, Y. L.; Mayr, U.; McGregor, E.; Troy, H.; Baier, G.; Leitges, M.; Dunn, M. J.; Griffiths, J. R.; Xu, Q.
Date of Publication (YYYY-MM-DD):2004-08
Title of Journal:Am J Physiol Heart Circ Physiol
Issue / Number:2
Start Page:H937
End Page:45
Review Status:Peer-review
Audience:Experts Only
Abstract / Description: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).
Free Keywords:Animals
; Magnetic Resonance Spectroscopy/diagnostic use
; Mice
; Mice, Knockout
; Molecular Chaperones/metabolism
; Myocardium/enzymology/*metabolism
; Peroxidases/metabolism
; Protein Kinase C/deficiency/*physiology
; Proteome/metabolism
; Research Support, Non-U.S. Gov't
External Publication Status:published
Document Type:Article
Affiliations:MPI für experimentelle Endokrinologie
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:1]