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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 559622.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Differential expression of protein kinase C isoforms in coronary arteries of diabetic mice lacking the G-protein Galpha11
Authors:Hoyer, D. P.; Korkmaz, Y.; Gronke, S.; Addicks, K.; Wettschureck, N.; Offermanns, S.; Reuter, H.
Title of Journal:Cardiovasc Diabetol
Volume:9
Start Page:93
Audience:Not Specified
Abstract / Description:BACKGROUND: Diabetes mellitus counts as a major risk factor for developing atherosclerosis. The activation of protein kinase C (PKC) is commonly known to take a pivotal part in the pathogenesis of atherosclerosis, though the influence of specific PKC isozymes remains unclear. There is evidence from large clinical trials suggesting excessive neurohumoral stimulation, amongst other pathways leading to PKC activation, as a central mechanism in the pathogenesis of diabetic heart disease. The present study was therefore designed to determine the role of Gq-protein signalling via Galpha11 in diabetes for the expression of PKC isozymes in the coronary vessels. METHODS: The role of Galpha11 in diabetes was examined in knockout mice with global deletion of Galpha11 compared to wildtype controls. An experimental type 1-diabetes was induced in both groups by injection of streptozotocin. Expression and localization of the PKC isozymes alpha, betaII, delta, epsilon, and zeta was examined by quantitative immunohistochemistry. RESULTS: 8 weeks after induction of diabetes a diminished expression of PKC epsilon was observed in wildtype animals. This alteration was not seen in Galpha11 knockout animals, however, these mice showed a diminished expression of PKCzeta. Direct comparison of wildtype and knockout control animals revealed a diminished expression of PKC delta and epsilon in Galpha11 knockout animals. CONCLUSION: The present study shows that expression of the nPKCs delta and epsilon in coronary vessels is under control of the g-protein Galpha11. The reduced expression of PKC zeta that we observed in coronary arteries from Galpha11-knockout mice compared to wildtype controls upon induction of diabetes could reduce apoptosis and promote plaque stability. These findings suggest a mechanism that may in part underlie the therapeutic benefit of RAS inhibition on cardiovascular endpoints in diabetic patients.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Internal Medicine III, University of Cologne, Kerpener Str, 62, 50937 Cologne, Germany.
Identifiers:ISSN:1475-2840 (Electronic) 1475-2840 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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