Resveratrol inhibits migration and Rac1 activation in EGF- but not PDGF-activated vascular smooth muscle cells

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Scope: Migration of vascular smooth muscle cells (VSMC) reflects one of the initial steps in atherosclerosis. Resveratrol (RV) is suggested to mediate putative vasoprotective properties of red wine leading to the hypothesis that RV interferes with growth factor-induced migration of VSMC.

Methods and results: We show here that RV (50 μM) strongly reduces epidermal growth factor (EGF)- but not platelet-derived growth factor (PDGF)-induced VSMC migration using the wound-healing technique. Accordingly, RV inhibited Rac1 activation and lamellipodia formation in response to EGF but not PDGF as shown by pull-down assays and fluorescence microscopy after actin staining with phalloidin-FITC, respectively. Since Src-family kinases and the phosphatidylinositol-3 kinase (PI3K) are reported to be crucial upstream mediators of Rac1 activation we examined the PI3K inhibitor wortmannin and the src kinase inhibitor SU6656 side-by-side with RV for their anti-migratory potential. Whereas src inhibition abrogated both EGF- and PDGF-triggered migration, wortmannin, like RV, was more effective in EGF- than PDGF-activated cells, suggesting that PI3K inhibition, previously shown for RV in growth factor-activated VSMC, contributes to the anti-migratory effect of RV in EGF-stimulated VSMC.

Conclusion: This study is the first to discover an anti-migratory potential of RV in EGF-activated VSMC that is most likely mediated via Rac1 inhibition.

Related collections

Most cited references 22

Record: found
Abstract: found
Article: not found

Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications.

C. Lastra, Isabel Villegas (2005)

Resveratrol is a phytoalexin polyphenolic compound found in various plants, including grapes, berries, and peanuts. Multiple lines of compelling evidence indicate its beneficial effects on neurological, hepatic, and cardiovascular systems. Also one of the most striking biological activities of resveratrol soundly investigated during the late years has been its cancer-chemopreventive potential. In fact, recently it has been demonstrated that this stilbene blocks the multistep process of carcinogenesis at various stages: tumor initiation, promotion, and progression. One of the possible mechanisms for its biological activities involves downregulation of the inflammatory response through inhibition of synthesis and release of pro-inflammatory mediators, modification of eicosanoid synthesis, inhibition of activated immune cells, or inhibiting such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via its inhibitory effects on nuclear factor (kappa)B (NF-(kappa)B) or the activator protein-1 (AP-1). More recent data provide interesting insights into the effect of this compound on the lifespan of yeast and flies, implicating the potential of resveratrol as an anti-aging agent in treating age-related human diseases. It is worthy to note that the phenolic compound possesses a low bioavailability and rapid clearance from the plasma. As the positive effects of resveratrol on inflammatory response regulation may comprise relevant clinical implications, the purpose of this article is to review its strong anti-inflammatory activity and the plausible mechanisms of these effects. Also, this review is intended to provide the reader an up-date of the bioavailability and pharmacokinetics of resveratrol and its impact on lifespan.

0 comments Cited 146 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Resveratrol: A molecule whose time has come? And gone?

George Soleas, Eleftherios P. Diamandis, David M. Goldberg (1997)

Resveratrol (3,5,4'-trihydroxystilbene) is the parent compound of a family of molecules, including glucosides and polymers, existing in cis and trans configurations in a narrow range of spermatophytes of which vines, peanuts and pines are the prime representatives. Its synthesis from p-coumaroyl CoA and malonyl CoA is induced by stress, injury, infection or UV-irradiation, and it is classified as a phytoalexin anti-fungicide conferring disease resistance in the plant kingdom. In vitro, ex vivo and animal experiments have shown that it possesses many biological attributes that favour protection against atherosclerosis, including antioxidant activity, modulation of hepatic apolipoprotein and lipid synthesis, inhibition of platelet aggregation as well as the production of pro-atherogenic eicosanoids by human platelets and neutrophils. Red wine represents its main source in the human diet, and it has been proposed as a major constituent of the polyphenol fraction to which the health benefits of red wine consumption have been attributed. The past several years have witnessed intense research devoted to its measurement in wine and the factors likely to promote its enrichment in this beverage. Up to the present, conclusive evidence for its absorption by human subjectsin biologically significant amounts is lacking, and it is questionable (but not yetexcluded) that its powerful and beneficial in vitro activities are reproduced as a consequence of sustained moderate red wine consumption.

0 comments Cited 113 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front.

Stefan Koestler, Eliza Small, Sonja Auinger … (2008)

Eukaryotic cells advance in phases of protrusion, pause and withdrawal. Protrusion occurs in lamellipodia, which are composed of diagonal networks of actin filaments, and withdrawal terminates with the formation of actin bundles parallel to the cell edge. Using correlated live-cell imaging and electron microscopy, we have shown that actin filaments in protruding lamellipodia subtend angles from 15-90 degrees to the front, and that transitions from protrusion to pause are associated with a proportional increase in filaments oriented more parallel to the cell edge. Microspike bundles of actin filaments also showed a wide angular distribution and correspondingly variable bilateral polymerization rates along the cell front. We propose that the angular shift of filaments in lamellipodia serves in adapting to slower protrusion rates while maintaining the filament densities required for structural support; further, we suggest that single filaments and microspike bundles contribute to the construction of the lamella behind and to the formation of the cell edge when protrusion ceases. Our findings provide an explanation for the variable turnover dynamics of actin filaments in lamellipodia observed by fluorescence speckle microscopy and are inconsistent with a current model of lamellipodia structure that features actin filaments branching at 70 degrees in a dendritic array.

0 comments Cited 69 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Mol Nutr Food Res

Journal ID (iso-abbrev): Mol Nutr Food Res

Journal ID (publisher-id): mnfr

Title: Molecular Nutrition & Food Research

Publisher: WILEY-VCH Verlag (Weinheim )

ISSN (Print): 1613-4125

ISSN (Electronic): 1613-4133

Publication date (Print): August 2011

Publication date (Electronic): 05 July 2011

Volume: 55

Issue: 8

Pages: 1230-1236

Affiliations

Department of Pharmacognosy, University of Vienna Vienna, Austria

Author notes

Correspondence: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria Fax: +43-1-4277-55969 E-mail: Verena.Dirsch@ 123456univie.ac.at Fax: 143-1-4277-55969

Article

DOI: 10.1002/mnfr.201100309

PMC ID: 3482936

PubMed ID: 21732534

SO-VID: 562b5d17-d8d7-4890-97eb-8391626f68ac

License:

Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

Resveratrol inhibits migration and Rac1 activation in EGF- but not PDGF-activated vascular smooth muscle cells

Read this article at

Abstract

Abstract

Related collections

Karger: Nutrition and Dietetics

Most cited references 22

Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications.

Resveratrol: A molecule whose time has come? And gone?

Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 615

Cited by 6

Most referenced authors 912