Universität zu Köln

Hoyer, Dieter Paul, Korkmaz, Yueksel, Groenke, Sabine, Addicks, Klaus, Wettschureck, Nina ORCID: 0000-0001-6858-1460, Offermanns, Stefan ORCID: 0000-0001-8676-6805 and Reuter, Hannes (2010). Differential expression of protein kinase C isoforms in coronary arteries of diabetic mice lacking the G-protein G alpha 11. Cardiovasc. Diabetol., 9. LONDON: BMC. ISSN 1475-2840

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Abstract

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 G(q)-protein signalling via G alpha(11) in diabetes for the expression of PKC isozymes in the coronary vessels. Methods: The role of G alpha(11) in diabetes was examined in knockout mice with global deletion of G alpha(11) 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, beta parallel to, delta, epsilon, and zeta was examined by quantitative immunohistochemistry. Results: 8 weeks after induction of diabetes a diminished expression of PKC e was observed in wildtype animals. This alteration was not seen in G alpha(11) knockout animals, however, these mice showed a diminished expression of PKC zeta. Direct comparison of wildtype and knockout control animals revealed a diminished expression of PKC d and e in G alpha(11) 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 G alpha(11). The reduced expression of PKC zeta that we observed in coronary arteries from G alpha(11)-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoyer, Dieter Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Korkmaz, Yueksel UNSPECIFIED UNSPECIFIED UNSPECIFIED Groenke, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Addicks, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wettschureck, Nina UNSPECIFIED orcid.org/0000-0001-6858-1460 UNSPECIFIED Offermanns, Stefan UNSPECIFIED orcid.org/0000-0001-8676-6805 UNSPECIFIED Reuter, Hannes UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-490362
DOI:	10.1186/1475-2840-9-93
Journal or Publication Title:	Cardiovasc. Diabetol.
Volume:	9
Date:	2010
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1475-2840
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SMOOTH-MUSCLE-CELLS; PKC-BETA-II; ENDOTHELIAL-CELLS; ANGIOTENSIN-II; PHORBOL ESTER; KAPPA-B; ACTIVATION; INHIBITION; EPSILON; APOPTOSIS Multiple languages Cardiac & Cardiovascular Systems; Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49036