This Article Full Text Full Text (PDF) Data Supplement 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 Gouni-Berthold, I. Articles by Sachinidis, A. Search for Related Content PubMed PubMed Citation Articles by Gouni-Berthold, I. Articles by Sachinidis, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Cell signalling/signal transduction Mechanism of atherosclerosis/growth factors

(Hypertension. 2001;38:1030.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Gangliosides GM1 and GM2 Induce Vascular Smooth Muscle Cell Proliferation via Extracellular Signal-Regulated Kinase 1/2 Pathway

Ioanna Gouni-Berthold; Claudia Seul; Yon Ko; Jürgen Hescheler; Agapios Sachinidis

From the Medizinische Universitäts-Poliklinik (I.G.-B., C.S., Y.K.), Bonn, Germany; and the Institute of Neurophysiology (J.H., A.S.), University of Cologne, Cologne, Germany.

Correspondence to Prof Dr Agapios Sachinidis, PhD, Institute of Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany. E-mail A.Sachinidis{at}uni-koeln.de

Abstract—— Gangliosides, sialic acid-containing glycophospholipids, accumulate in atherosclerotic vessels and appear to regulate the proliferation of various cell types. Furthermore, vascular smooth muscle cell (VSMC) proliferation is associated with the development and progression of cardiovascular diseases. To demonstrate whether gangliosides are able to modulate the VSMC growth, the effect of gangliosides GM1, GM2, and GM3 on cell DNA synthesis and cell number has been examined. Moreover, we investigated possible intracellular mechanisms by which GM1 and GM2 elicit their mitogenic effects. Stimulation of VSMCs with GM1 and GM2 resulted in a dose-dependent increase in DNA synthesis and cell number, whereas GM3 caused a decrease in DNA synthesis. GM1 and GM2 (50 µmol/L) stimulate phosphorylation of extracellular signal-regulated kinases (ERKs) 1 and 2 and phosphorylation of the c-Jun N-terminal kinase (JNK), with a maximum at 15 minutes, but they do not have an effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). GM3 (50 µmol/L), on the other hand, does not stimulate any of the 3 aforementioned MAPKs. Pretreatment of the cells with 20 µmol/L PD 098,059 caused a complete inhibition of ERK1/2 and JNK MAPK, whereas pretreatment with a Ras (farnesyl transferase) inhibitor did not abrogate the GM1- and GM2-induced ERK1/2 phosphorylation. Furthermore, GM1 and GM2 did not activate Raf-1 kinase. Interestingly, pretreatment of VSMCs with 100 nmol/L pertussis toxin resulted in a complete inhibition of the ERK1/2 phosphorylation. Finally, the GM1- and GM2-induced increase in cell number was significantly inhibited by PD 098,059. We may conclude that GM1 and GM2 stimulate ERK1/2 via a pertussis toxin-sensitive G_i-coupled receptor through a Raf-1 kinase-independent pathway. Moreover, the GM1- and GM2-induced VSMC growth is ERK1/2 dependent.

Key Words: lipids • protein kinases • phosphorylation • growth substances • cardiovascular diseases

This article has been cited by other articles:

				S.-K. Moon, S.-K. Kang, and C.-H. Kim Reactive oxygen species mediates disialoganglioside GD3-induced inhibition of ERK1/2 and matrix metalloproteinase-9 expression in vascular smooth muscle cells FASEB J, July 1, 2006; 20(9): 1387 - 1395. [Abstract] [Full Text] [PDF]

				D. Seo, T. Wang, H. Dressman, E. E. Herderick, E. S. Iversen, C. Dong, K. Vata, C. A. Milano, F. Rigat, J. Pittman, et al. Gene Expression Phenotypes of Atherosclerosis Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1922 - 1927. [Abstract] [Full Text] [PDF]

				Y. Liu, R. Li, and S. Ladisch Exogenous Ganglioside GD1a Enhances Epidermal Growth Factor Receptor Binding and Dimerization J. Biol. Chem., August 27, 2004; 279(35): 36481 - 36489. [Abstract] [Full Text] [PDF]

				S.-K. Moon, H.-M. Kim, Y.-C. Lee, and C.-H. Kim Disialoganglioside (GD3) Synthase Gene Expression Suppresses Vascular Smooth Muscle Cell Responses via the Inhibition of ERK1/2 Phosphorylation, Cell Cycle Progression, and Matrix Metalloproteinase-9 Expression J. Biol. Chem., August 6, 2004; 279(32): 33063 - 33070. [Abstract] [Full Text] [PDF]

				O. S. Kim, E. J. Park, E.-h. Joe, and I. Jou JAK-STAT Signaling Mediates Gangliosides-induced Inflammatory Responses in Brain Microglial Cells J. Biol. Chem., October 18, 2002; 277(43): 40594 - 40601. [Abstract] [Full Text] [PDF]