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RGD Peptide (rgd + peptide)

Distribution by Scientific Domains

Medical Sciences	56%
Life Sciences	25%
Chemistry	18%

Selected Abstracts

Cytoprotective Effects of a Cyclic RGD Peptide in Steatotic Liver Cold Ischemia and Reperfusion Injury

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
C. Fondevila
The serious need for expanding the donor population has attracted attention to the use of steatotic donor livers in orthotopic liver transplantation (OLT). However, steatotic livers are highly susceptible to hepatic ischemia,reperfusion injury (IRI). Expression of fibronectin (FN) by endothelial cells is an important feature of hepatic response to injury. We report the effect of a cyclic RGD peptide with high affinity for the ,5,1, the FN integrin receptor, in a rat model of steatotic liver cold ischemia, followed by transplantation. RGD peptide therapy ameliorated steatotic IRI and improved the recipient survival rate. It significantly inhibited the recruitment of monocyte/macrophages and neutrophils, and depressed the expression of pro-inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and interferon (IFN)-,. Moreover, it resulted in profound inhibition of metalloproteinase-9 (MMP-9) expression, a gelatinase implied in leukocyte migration in damaged livers. Finally, we show that RGD peptide therapy reduced the expression of the 17-kDa active caspase-3 and the number of apoptotic cells in steatotic OLTs. The observed protection against steatotic liver IRI by the cyclic RGD peptides with high affinity for the ,5,1 integrin suggests that this integrin is a potential therapeutic target to allow the successful utilization of marginal steatotic livers in transplantation. [source]

CMR 2005: 3.03: New RGD peptide-based molecular imaging agents for detection of angiogenesis

CONTRAST MEDIA & MOLECULAR IMAGING, Issue 2 2006
B. Indrevoll
[source]

Hypoxia stimulates the autocrine regulation of migration of vascular smooth muscle cells via HIF-1,-dependent expression of thrombospondin-1

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008
Mayuko Osada-Oka
Abstract The migration of vascular smooth muscle cells from the media to intima and their subsequent proliferation are critical causes of arterial wall thickening. In atherosclerotic lesions increases in the thickness of the vascular wall and the impairment of oxygen diffusion capacity result in the development of hypoxic lesions. We investigated the effect of hypoxia on the migration of human coronary artery smooth muscle cells (CASMCs) via HIF-1,-dependent expression of thrombospondin-1 (TSP-1). When the cells were cultured under hypoxic conditions, mRNA and protein levels of TSP-1, and mRNA levels of integrin ,3 were increased with the increase in HIF-1, protein. DNA synthesis and migration of the cells were stimulated under the conditions, and a neutralizing anti-TSP-1 antibody apparently suppressed the migration, but not DNA synthesis. The migration was also inhibited by RGD peptide that binds to integrin ,3. Furthermore, the migration was completely suppressed in HIF-1,-knockdown cells exposed to hypoxia, while it was significantly enhanced in HIF-1,-overexpressing cells. These results suggest that the hypoxia induces the migration of CASMCs, and that the migration is elicited by TSP-1 of which induction is fully dependent on the stabilization of HIF-1,, in autocrine regulation. Thus we suggest that HIF-1, plays an important role in the pathogenesis of atherosclerosis. J. Cell. Biochem. 104: 1918,1926, 2008. © 2008 Wiley-Liss, Inc. [source]

BNP-induced activation of cGMP in human cardiac fibroblasts: Interactions with fibronectin and natriuretic peptide receptors

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006
Brenda K. Huntley
Cardiac remodeling involves the accumulation of extracellular matrix (ECM) proteins including fibronectin (FN). FN contains RGD motifs that bind integrins at DDX sequences allowing signaling from the ECM to the nucleus. We noted that the natriuretic peptide receptor A (NPR-A) sequence contains both RGD and DDX sequences. The goal of the current investigation was to determine potential interactions between FN and NPR-A on BNP induction of cGMP in cultured human cardiac fibroblasts (CFs). Further, we sought to determine whether a Mayo designed NPR-A specific RGD peptide could modify this interaction. Here we reconfirm the presence of all three natriuretic peptide receptors (NPR) in CFs. CFs plated on FN demonstrated a pronounced increase in cGMP production to BNP compared to non-coated plates. This production was also enhanced by the NPR-A specific RGD peptide, which further augmented FN associated cGMP production. Addition of HS-142-1, a NPR-A/B antagonist, abrogated the responses of BNP to both FN and the NPR-A specific RGD peptide. Finally, we defined a possible role for the NPR-C through non-cGMP mechanisms in mediating the anti-proliferative actions of BNP in CFs where the NPR-C antagonist cANF 4-28 but not HS-142-1 blocked BNP-mediated inhibition of proliferation of CFs. We conclude that NPR-A interacts with components of the ECM such as FN to enhance BNP activation of cGMP and that a small NPR-A specific RGD peptide augments this action of BNP with possible therapeutic implications. Lastly, the NPR-C may also have a role in mediating anti-proliferative actions of BNP in CFs. J. Cell. Physiol. 209: 943,949, 2006. © 2006 Wiley-Liss, Inc. [source]

Cell adhesion molecules for targeted drug delivery

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2006
Alison L. Dunehoo
Abstract Rapid advancement of the understanding of the structure and function of cell adhesion molecules (i.e., integrins, cadherins) has impacted the design and development of drugs (i.e., peptide, proteins) with the potential to treat cancer and heart and autoimmune diseases. For example, RGD peptides/peptidomimetics have been marketed as anti-thrombic agents and are being investigated for inhibiting tumor angiogenesis. Other cell adhesion peptides derived from ICAM-1 and LFA-1 sequences were found to block T-cell adhesion to vascular endothelial cells and epithelial cells; these peptides are being investigated for treating autoimmune diseases. Recent findings suggest that cell adhesion receptors such as integrins can internalize their peptide ligands into the intracellular space. Thus, many cell adhesion peptides (i.e., RGD peptide) were used to target drugs, particles, and diagnostic agents to a specific cell that has increased expression of cell adhesion receptors. This review is focused on the utilization of cell adhesion peptides and receptors in specific targeted drug delivery, diagnostics, and tissue engineering. In the future, more information on the mechanism of internalization and intracellular trafficking of cell adhesion molecules will be exploited for delivering drug molecules to a specific type of cell or for diagnosis of cancer and heart and autoimmune diseases. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1856,1872, 2006 [source]

Generation of fiber-modified adenovirus vectors containing heterologous peptides in both the HI loop and C terminus of the fiber knob

THE JOURNAL OF GENE MEDICINE, Issue 4 2003
Naoya Koizumi
Abstract Background Fiber-modified adenovirus (Ad) vectors can be effective in overcoming the limitations of conventional Ad vectors, specifically their inefficient gene transfer into cells lacking the primary receptor, the coxsackievirus and adenovirus receptor (CAR). Several types of fiber-modified Ad vectors have been developed. In this study, we evaluated the functionality of several fiber-modified Ad vectors. Methods We developed a simple method based on in vitro ligation to construct Ad vectors containing heterologous foreign peptides in both the HI loop and C terminus of the fiber knob. A functional comparison of Ad vectors containing RGD and/or K7 (KKKKKKK) peptide in the HI loop or C terminus of the fiber knob was performed in several types of human, mouse, and rat cells, including CAR-positive and -negative cells, and tumor cells in mice in vivo. Results In the case of the in vitro experiment, Ad vectors containing RGD peptide in the HI loop of the fiber knob showed a higher level of gene transfer than vectors containing RGD peptide at the C terminus of the fiber knob. Ad vectors containing K7 peptide at the C terminus of the fiber knob showed levels of gene transfer similar to those of Ad vectors containing RGD peptide in the HI loop of the fiber knob, depending on the cell type. Ad vectors containing both peptides in the HI loop or C terminus of the fiber knob showed the highest levels of gene transfer and a broader tropism. For gene transfer into tumor cells in vivo, the Ad vectors containing RGD peptide were the most efficient. Conclusions In the experiment using cultured cells, Ad vectors containing both RGD and K7 peptides were the most efficient with a broader tropism. In contrast, in the experiment in vivo, Ad vectors containing RGD peptide in the HI loop of the fiber knob were more efficient than the vectors containing K7 peptide (including double-modified vectors containing both the RGD and K7 peptides). These comparative analyses could provide a systemic reference for the use of fiber-modified Ad vectors. Our simple method, in which the peptide of interest can be expressed in Ad vectors in either the HI loop or the C terminus of the fiber knob, or both, could be a powerful tool for gene transfer into mammalian cells in studies of gene function as well as in gene therapy. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Cytoprotective Effects of a Cyclic RGD Peptide in Steatotic Liver Cold Ischemia and Reperfusion Injury

Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs

ARTHRITIS & RHEUMATISM, Issue 2 2009
Christine Lyn Le Maitre
Objective Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with ,5,1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved. Methods Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the ,5,1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real-time quantitative polymerase chain reaction. Results Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the ,5,1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue. Conclusion Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the ,5,1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins. [source]

Matrix Regulation of Skeletal Cell Apoptosis II: Role of Arg-Gly-Asp-Containing Peptides

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2002
Robert L. Perlot Jr.
Abstract This investigation was based on the assumption that arg-gly-asp (RGD)-containing peptides are released from the extracellular matrix of bone and cartilage during the remodeling cycle. We asked the question: Can RGD peptides influence skeletal cell viability? Primary human osteoblasts, mouse MC-3T3-E1 cells, and chick chondrocytes were incubated with purified RGD-containing peptides and cell viability was determined. The RGD peptide did not kill osteoblasts, chondrocytes, or MC-3T3-E1 cells. In contrast, RGDS and GRGDSP peptides killed all three cell types. Osteoblast death was quite rapid, occurring within 6 h of treatment. transferase uridyl mediated nick end labeling (TUNEL) and transmission electron microscopy (TEM) analysis indicated that death was mediated by apoptosis. To learn if mitochondria transduced the death signal, cells were treated with RGDS and organelle function was evaluated using a voltage-sensitive fluorescent probe. It was observed that there was no net loss of fluorescence and, hence, it was concluded that mitochondria were not the primary effectors of the apoptotic response. Experiments were performed with enzyme inhibitors to determine the import of the caspase pathway on RGDS-mediated osteoblast apoptosis. Results of these studies, as well as a study conducted using a fluorescent substrate, pointed to caspase 3 mediating the effector stage of the apoptotic process. Finally, using a purified labeled-RGDS peptide, we showed that the molecule was not restricted by the plasma membrane because it was accumulated in the cytosolic compartment. Results of the investigation support the view that resorption of the extracellular matrix generates peptide products that can induce apoptosis of vicinal cells. [source]

The relative orientation of the Arg and Asp side chains defined by a pseudodihedral angle as a key criterion for evaluating the structure,activity relationship of RGD peptides

JOURNAL OF PEPTIDE SCIENCE, Issue 8 2004
Sarantos Kostidis
Abstract The ability of an integrin to distinguish between the RGD-containing extracellular matrix proteins is thought to be due partially to the variety of RGD conformations. Three criteria have been proposed for the evaluation of the structure,activity relationship of RGD-containing peptides. These include: (i) the distance between the charged centres, (ii) the distance between the Arg C, and Asp C, atoms, and (iii) the pseudo-dihedral angle defining the Arg and Asp side-chain orientation formed by the Arg C,, Arg C,, Asp C, and Asp C, atoms. A comparative conformation,activity study was performed between linear RGD peptides and strongly constrained cyclic (S,S) -CDC- bearing compounds, which cover a wide range of inhibition potency of platelet aggregation. It is concluded that the fulfilment of the ,45° , pseudo-dihedral angle , +45° criterion is a prerequisite for an RGD compound to exhibit inhibitory activity. Once this criterion is accomplished, the longer the distance between the charged centres and/or between the Arg and Asp C, atoms, the higher is the biological activity. In addition, the stronger the ionic interaction between Arg and Asp charged side chains, the lower the anti-aggregatory activity. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source]

Cytoprotective Effects of a Cyclic RGD Peptide in Steatotic Liver Cold Ischemia and Reperfusion Injury

Expression of Integrin ,v,3 in Gliomas Correlates with Tumor Grade and Is not Restricted to Tumor Vasculature

BRAIN PATHOLOGY, Issue 3 2008
Oliver Schnell MD
Abstract In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of ,v,3 integrin caused by malignancy. The aim of our study was to assess the extent and pattern of ,v,3 integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of ,v,3 integrin and quantified by an imaging software. The expression of ,v,3 was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of ,v,3 integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the ,3 integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of ,v,3 integrin in gliomas and are of relevance for the inhibition of ,v,3 integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth. [source]

Effect of RGD peptide coating of titanium implants on periimplant bone formation in the alveolar crest

CLINICAL ORAL IMPLANTS RESEARCH, Issue 3 2002
An experimental pilot study in dogs
Abstract: The aim of the present study was to analyse the effect of organic coating of titanium implants on periimplant bone formation and bone/implant contact. Three types of implants were used: (i) Ti6Al4V implants with polished surface (control 1) (ii) Ti6Al4V implants with collagen coating (control 2) (iii) Ti6Al4V implants with collagen coating and covalently bound RGD peptides. All implants had square cross-sections with an oblique diameter of 4.6 mm and were inserted press fit into trephine burr holes of 4.6 mm in the mandibles of 10 beagle dogs. The implants of five animals each were evaluated after a healing period of 1 month and 3 months, during which sequential fluorochrome labelling of bone formation was performed. Bone formation was evaluated by morphometric measurement of the newly formed bone around the implant and the percentage of implant bone contact. After 1 month there was only little bone/implant contact, varying between 2.6 and 6.7% in the cortical bone and 4.4 and 5.7% in the cancellous bone, with no significant differences between the three types of implants. After 3 months, implants with polished surfaces exhibited 26.5 and 31.2% contact in the cortical and cancellous bone, respectively, while collagen-coated implants had 19.5 and 28.4% bone contact in these areas. Implants with RGD coating showed the highest values with 42.1% and 49.7%, respectively. Differences between the surface types as such were not significant, but the increase in bone/implant contact from 1 to 3 months postoperatively was significant only in the group of RGD-coated implants (P = 0.008 and P = 0.000). The results of this pilot study thus provide only weak evidence that coating of titanium implants with RGD peptides in the present form and dosage may increase periimplant bone formation in the alveolar process. The results therefore require further verification in a modified experimental setting. Résumé Le but de l'étude présente a été d'évaluer l'effet d'un recouvrement organique des implants en titane sur la formation osseuse paro?mplantaire et le contact os/implant. Trois types d'implants ont été utilisés: 1) implants Ti6AI4V avec surface polie (contrôle 1), 2) implants Ti6AI4V avec recouvrement de collagène (contrôle 2), 3) implants Ti6aI4V avec recouvrement de collagène et des peptides RGD accrochés de manière covalente. Tous les implants avaient une section carrée avec un diamètre oblique de 4.6 mm et étaient insérés dans des trous percés à l'aide de trépans de 4.6 mm dans la mandibule de dix chiens beagle. Les implants de cinq animaux ont étéévalués après une période de guérison d'un mois et de trois mois durant laquelle un marquage fluochrome séquentiel de la néoformation osseuse a été effectué. La formation osseuse a étéévaluée par mesure morphométrique de l'os néoformé autour de l'implant et par pourcentage de contact os/implant. Après un mois, il n'y avait que peu de contact os/implant, variant entre 2.6 et 6.7% dans l'os cortical et 4.4 et 5.7% dans l'os spongieux, sans aucune différence significative entre les trois types d'implants. Après trois mois, les implants avec les surfaces polies montraient respectivement 26.5 et 31.2% d'os cortical et spongieux, tandis que les implants recouverts de collagène avaient 19.5 et 28.4% de contact osseux dans ces zones. Les implants avec le recouvrement RGD avaient les valeurs les plus importantes avec respectivement 42.1% et 49.7%. Les différences entre les types de surface n'étaient pas significatives mais l'augmentation du contact os/implant de 1 à 3 mois après l'opération n'était significative que dans le groupe RGD (P=0.008 et P=0.0000). Les résultats de cette ewtude pilote n'ont donc mis en évidence qu'une maigre preuve que les recouvrements des implants en titane par les petpides RGD sous la forme présente et le dosage présent, pouvaient augmenter la formation osseuse paro?mplantaire dans le processus alvéolaire. Ces résultats requièrent donc davantage de vérifications dans un système expérimental modifié. Zusammenfassung Es war das Ziel dieser Untersuchung, den Einfluss einer organischen Beschichtung von Titanimplantaten auf die periimplantäre Knochenformation und auf den KnochenImplantatkontakt zu analysieren. Drei Typen von Implantaten wurden verwendet: i) Ti6AI4V Implantate mit polierter Oberfläche (Kontrolle 1), ii) Ti6AI4V Implantate mit Kollagenbeschichtung (Kontrolle 2), iii) Ti6AI4V Implantate mit Kollagenbeschichtung und kovalent gebundenen RGD-Peptiden. Alle Implantate hatten einen quadratischen Querschnitt mit einem Querdurchmesser von 4.6 mm. Sie wurden in die Unterkiefer von zehn Beaglehunden in zylindrische Bohrungen mit einem Durchmesser von 4.6 mm mit Pressitz eingesetzt. Die Implantate von je funf Tieren wurden nach einer Helungszeit von einem bzw. drei Monaten ausgewertet. Während der gesamten Zeit wurden sequentielle Fluorochrommarkierungen der Knochenbildung durchgeführt. Die Knochenbildung wurde durch morphometrische Messungen des neugebildeten Knochens um die Implantate und durch Messungen der prozentualen Anteile des Knochen-/Implantatkontakts ausgewertet. Nach 1 Monat war nur wenig Knochen-/Implantatkontakt vorhanden. Er variierte zwischen 2.6 und 6.7% im kortikalen Knochen und zwischen 4.4 und 5.7% im spongiösen Knochen. Zwischen den drei Implantattypen bestanden keine signifikanten Unterschiede. Nach drei Monaten zeigten die Implantate mit polierten Oberflächen 26.5% Knochenkontakt im kortikalen bzw. 31.2% im spongiösen Knochen, während die kollagenbeschichteten Implantate 19.5% und 28.4% Knochenkontakt in diesen Regionen zeigten. Implantate mit RGD-Beschichtung zeigten mit 42.1% bzw. 49.7% die höchsten Werte. Zwischen den Oberflächentypen bestanden keine signifikanten Unterschiede. Nur in der Gruppe mit RGD-beschichteten Implantaten nahm der Knochen-/Implantatkontakt zwischen 1 bis 3 Monaten nach Chirurgie signifikant zu (P=0.008 und P=0.000). Die Resultate dieser zeigen nur mit schwacher Evidenz, dass die Beschichtung von Titanimplantaten mit RGD-Peptiden in der vorliegenden Form und Dosierung die periimplantäre Knochenformation im Alveolarkamm erhöht. Die Resultate müssen daher in einem modifizerten experimentellen Aufbau verifiziert werden. Resumen La intención del presente estudio fue analizar el efecto de la cobertura orgánica de implantes de titanio en la formación de hueso y contacto hueso/implante. Se usaron tres tipos de implantes: i) implantes de Ti6AI4V con superficie pulida (control 1), ii) implantes Ti6AI4V con cubierta de colágeno (control 2), iii) implantes de Ti6AI4V con cubierta de colágeno y péptidos RGD con unión convalente. Todos los implantes tenían secciones cuadradas con un diámetro oblicuo de 4.6 mm y se insertaron a presión en orificios trepanados de 4.6 mm en las mandíbulas de 10 perros beagle. Se evaluaron los implantes de 5 animales tras un periodo de cicatrización de un mes y tres meses los otros cinco, durante este tiempo se llevó a cabo marcado secuencial con fluorocromo de la formación de hueso. La formación de hueso se evaluó mediante mediciones morfométricas del hueso neoformado alrededor del implante y el porcentaje de contacto hueso implante. Tras 1 mes existió muy poco contacto hueso/implante variando entre 2.6 y 6.7% en el hueso cortical y 4.4 y 5.7% en el hueso esponjoso sin diferencias significativas entre los tres tipos de implantes. Tras tres meses, los implantes con superficies pulidas exhibieron un 26.5 y 31.2% en el hueso cortical y esponjoso, respectivamente, mientras que los implantes con cubiertas de colágeno tuvieron un 19.5 y un 28.4% de contacto óseo en estas áreas. Los implantes con cubiertas de RGD mostraron los valores más altos con un 42.1 y un 49.7% respectivamente. Las diferencias ente tipos de superficie como tales no fueron significativas pero el incremento de contacto hueso/implante de 1 a 3 meses tras la operación fue significativo solo en el grupo de implantes con cubierta RGD (P=0.008 y P=0.000). Los resultados de este estudio piloto aunque han mostrado solo una débil evidencia, que la cobertura de implantes de titanio con péptidos RGD en la forma y dosis presente pueden incrementar la formación de hueso periimplantario en el proceso alveolar. Los resultados, por lo tanto, requieren una posterior verificación en una situación experimental modificada. [source]