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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4180-4187. Prepublished online as a Blood First Edition Paper on February 24, 2004; DOI 10.1182/blood-2003-06-2144. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2144v1 103/11/4180    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Aguzzi, M. S. Articles by Facchiano, A. Search for Related Content PubMed PubMed Citation Articles by Aguzzi, M. S. Articles by Facchiano, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Apoptosis Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells Maria Simona Aguzzi, Claudia Giampietri, Francesco De Marchis, Fabrizio Padula, Roberto Gaeta, Gianluca Ragone, Maurizio C. Capogrossi, and Antonio Facchiano From the Laboratorio Patologia Vascolare and the Laboratorio Oncogenesi Molecolare, Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy; Dipartimento Istologia ed Embriologia Medica, Istituto Pasteur-Fondazione Cenci-Bolognetti University La Sapienza, Rome, Italy; the Divisione di Cardiochirurgia, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) "San Matteo," Pavia, Italy; and the Cattedra di Cardiochirurgia, University of Messina, Messina, Italy. Peptides containing the Arg-Gly-Asp (RGD) motif inhibit cell adhesion and exhibit a variety of other biologic effects including anticoagulant and antimetastatic activities. The aim of the present study was to examine the anchorage-independent effects of an RGD-containing peptide, Arg-Gly-Asp-Ser (RGDS), on human umbilical vein endothelial cells (HUVECs). Assays were performed on HUVECs seeded onto collagen IV; under these experimental conditions RGDS did not exert antiadhesive effects but significantly reduced FGF-2-dependent chemotaxis after 4 hours of treatment and reduced proliferation after 24 hours of treatment. Experiments carried out with caspase-specific inhibitors indicated that the observed antichemotactic effects required caspase 8 and caspase 9 activation. RGDS activated both caspase 8 and caspase 9 after 4 hours of treatment and caspase 3 after 24 hours of treatment, and markedly enhanced HUVEC apoptosis by transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)/Hoechst staining and fluorescence-activated cell sorting (FACS) analysis. Finally, confocal microscopy showed that RGDS localizes in the cytoplasm of live HUVECs within 4 hours and in vitro experiments showed that RGDS directly interacts with recombinant caspases 8 and 9 in a specific way. In summary, these results indicate that RGDS directly binds and activates caspases 8 and 9, inhibits chemotaxis, and induces apoptosis of HUVECs with a mechanism independent from its antiadhesive effect. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Maubant, D. Saint-Dizier, M. Boutillon, F. Perron-Sierra, P. J. Casara, J. A. Hickman, G. C. Tucker, and E. Van Obberghen-Schilling Blockade of {alpha}vbeta3 and {alpha}vbeta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells Blood, November 1, 2006; 108(9): 3035 - 3044. [Abstract] [Full Text] [PDF] D. Faraone, M. S. Aguzzi, G. Ragone, K. Russo, M. C. Capogrossi, and A. Facchiano Heterodimerization of FGF-receptor 1 and PDGF-receptor-{alpha}: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells Blood, March 1, 2006; 107(5): 1896 - 1902. [Abstract] [Full Text] [PDF] A. Capello, E. P. Krenning, B. F. Bernard, W. A.P. Breeman, J. L. Erion, and M. de Jong Anticancer Activity of Targeted Proapoptotic Peptides J. Nucl. Med., January 1, 2006; 47(1): 122 - 129. [Abstract] [Full Text] [PDF] L. J. Hofland, A. Capello, E. P. Krenning, M. de Jong, and M. P. van Hagen Induction of Apoptosis with Hybrids of Arg-Gly-Asp Molecules and Peptides and Antimitotic Effects of Hybrids of Cytostatic Drugs and Peptides J. Nucl. Med., January 1, 2005; 46(1_suppl): 191S - 198S. [Abstract] [Full Text] [PDF]

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