This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 94/10/e87    most recent 01.RES.0000131496.49135.1dv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mayr, M. Articles by Xu, Q. Search for Related Content PubMed PubMed Citation Articles by Mayr, M. Articles by Xu, Q. Related Collections Animal models of human disease Energy metabolism Functional genomics Genetically altered mice Smooth muscle proliferation and differentiation Mechanism of atherosclerosis/growth factors

(Circulation Research. 2004;94:e87.)
© 2004 American Heart Association, Inc.

UltraRapid Communications

Proteomic and Metabolomic Analysis of Vascular Smooth Muscle Cells

Role of PKC

Manuel Mayr, Richard Siow, Yuen-Li Chung, Ursula Mayr, John R. Griffiths, Qingbo Xu

From the Department of Cardiac and Vascular Sciences (M.M., U.M., Q.X.) and Department of Basic Medical Sciences (Y.-L.C., J.R.G.), St George’s Hospital Medical School, London, UK; and Centre for Cardiovascular Biology and Medicine (R.S.), King’s College, London, UK.

Correspondence to Prof Qingbo Xu, Department of Cardiac and Vascular Sciences, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. E-mail q.xu{at}sghms.ac.uk

Recent developments of proteomic and metabolomic techniques provide powerful tools for studying molecular mechanisms of cell function. Previously, we demonstrated that neointima formation was markedly increased in vein grafts of PKC-deficient mice compared with wild-type controls. To clarify the underlying mechanism, we performed a proteomic and metabolomic analysis of cultured vascular smooth muscle cells (SMCs) derived from PKC^+/+ and PKC^–/– mice. Using 2-dimensional electrophoresis and mass spectrometry, we identified >30 protein species that were altered in PKC^–/– SMCs, including enzymes related to glucose and lipid metabolism, glutathione recycling, chaperones, and cytoskeletal proteins. Interestingly, nuclear magnetic resonance spectroscopy confirmed marked changes in glucose metabolism in PKC^–/– SMCs, which were associated with a significant increase in cellular glutathione levels resulting in resistance to cell death induced by oxidative stress. Furthermore, PKC^–/– SMCs overexpressed RhoGDI, an endogenous inhibitor of Rho signaling pathways. Inhibition of Rho signaling was associated with a loss of stress fiber formation and decreased expression of SMC differentiation markers. Thus, we performed the first combined proteomic and metabolomic study in vascular SMCs and demonstrate that PKC is crucial in regulating glucose and lipid metabolism, controlling the cellular redox state, and maintaining SMC differentiation.

Key Words: proteomics • metabolomics • smooth muscle cells • PKC • signal transduction

This article has been cited by other articles:

				M. Mayr, D. Grainger, U. Mayr, A. S. Leroyer, G. Leseche, A. Sidibe, O. Herbin, X. Yin, A. Gomes, B. Madhu, et al. Proteomics, Metabolomics, and Immunomics on Microparticles Derived From Human Atherosclerotic Plaques Circ Cardiovasc Genet, August 1, 2009; 2(4): 379 - 388. [Abstract] [Full Text] [PDF]

				G. Pula, U. Mayr, C. Evans, M. Prokopi, D. S. Vara, X. Yin, Z. Astroulakis, Q. Xiao, J. Hill, Q. Xu, et al. Proteomics Identifies Thymidine Phosphorylase As a Key Regulator of the Angiogenic Potential of Colony-Forming Units and Endothelial Progenitor Cell Cultures Circ. Res., January 2, 2009; 104(1): 32 - 40. [Abstract] [Full Text] [PDF]

				M. Mayr Metabolomics: Ready for the Prime Time? Circ Cardiovasc Genet, October 1, 2008; 1(1): 58 - 65. [Full Text] [PDF]

				M. Mayr, A. Zampetaki, A. Sidibe, U. Mayr, X. Yin, A. I. De Souza, Y.-L. Chung, B. Madhu, P. H. Quax, Y. Hu, et al. Proteomic and Metabolomic Analysis of Smooth Muscle Cells Derived From the Arterial Media and Adventitial Progenitors of Apolipoprotein E-Deficient Mice Circ. Res., May 9, 2008; 102(9): 1046 - 1056. [Abstract] [Full Text] [PDF]

				H. Nakashima, G. D. Frank, H. Shirai, A. Hinoki, S. Higuchi, H. Ohtsu, K. Eguchi, A. Sanjay, M. E. Reyland, P. J. Dempsey, et al. Novel Role of Protein Kinase C-{delta} Tyr311 Phosphorylation in Vascular Smooth Muscle Cell Hypertrophy by Angiotensin II Hypertension, February 1, 2008; 51(2): 232 - 238. [Abstract] [Full Text] [PDF]

				K. K. Maddali, D. H. Korzick, D. L. Tharp, and D. K. Bowles PKC{delta} Mediates Testosterone-induced Increases in Coronary Smooth Muscle Cav1.2 J. Biol. Chem., December 30, 2005; 280(52): 43024 - 43029. [Abstract] [Full Text] [PDF]

				M. Mayr, Y.-L. Chung, U. Mayr, X. Yin, L. Ly, H. Troy, S. Fredericks, Y. Hu, J. R. Griffiths, and Q. Xu Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2135 - 2142. [Abstract] [Full Text] [PDF]

				H. Ohtsu, M. Mifune, G. D. Frank, S. Saito, T. Inagami, S. Kim-Mitsuyama, Y. Takuwa, T. Sasaki, J. D. Rothstein, H. Suzuki, et al. Signal-Crosstalk Between Rho/ROCK and c-Jun NH2-Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1831 - 1836. [Abstract] [Full Text] [PDF]

				M. Mayr, K. Mandal, Q. Xu, J. S. Lindholt, J. Stovring, S. Urbonavicius, E. W. Henneberg, L. Ostergaard, B. Honore, and H. Vorum Pitfalls of Proteomics * Response Circulation, September 21, 2004; 110(12): e316 - e316. [Full Text] [PDF]