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G Bellon

Publications and source records attributed to G Bellon.

At least 37 records · Page 2Linked to original sources
PubMed2001

Involvement of fibronectin type II repeats in the efficient inhibition of gelatinases A and B by long-chain unsaturated fatty acids.

The matrix metalloproteinases gelatinase A (MMP-2) and gelatinase B (MMP-9) are implicated in the physiological and pathological breakdown of several extracellular matrix proteins. In the present study, we show that long-chain fatty acids (e.g. oleic acid, elaidic acid, and cis- and trans-parinaric acids) inhibit gelatinase A as well as gelatinase B with K(i) values in the micromolar range but had only weak inhibitory effect on collagenase-1 (MMP-1), as assessed using synthetic or natural substrates. The inhibition of gelatinases depended on fatty acid chain length (with C18 > C16, C14, and C10), and the presence of unsaturations increased their inhibitory capacity on both types of gelatinase. Ex vivo experiments on human skin tissue sections have shown that micromolar concentrations of a long-chain unsaturated fatty acid (elaidic acid) protect collagen and elastin fibers against degradation by gelatinases A and B, respectively. In order to understand why gelatinases are more susceptible than collagenase-1 to inhibition by long-chain fatty acids, the possible role of the fibronectin-like domain (a domain unique to gelatinases) in binding inhibitory fatty acids was investigated. Affinity and kinetic studies with a recombinant fibronectin-like domain of gelatinase A and with a recombinant mutant of gelatinase A from which this domain had been deleted pointed to an interaction of long-chain fatty acids with the fibronectin-like domain of the protease. Surface plasmon resonance studies on the interaction of long-chain fatty acids with the three individual type II modules of the fibronectin-like domain of gelatinase A revealed that the first type II module is primarily responsible for binding these compounds.

Collagen↗
PubMed2000

Regulation of tumor cell chemotaxis by type IV collagen is mediated by a Ca(2+)-dependent mechanism requiring CD47 and the integrin alpha(V)beta(3).

Studies from our laboratories demonstrated that synthetic peptides from the non-collagenous (NC-1) domain of the alpha3 (IV) chain of type IV collagen (COL IV) enhanced tumor cell adhesion (Han, J., Ohno, N., Monboisse, J. C., Pasco, S., Borel, J. P., and Kefalides, N. A. (1997) J. Biol. Chem. 272, 20395-20401). We have isolated the receptors for the alpha3(IV)185-203 peptide from melanoma and prostate tumor cells and identified them as CD47/integrin-associated protein and the integrin alpha(V)beta(3) (Shahan, T. A., Ziaie, Z., Pasco, S., Fawzi, A., Bellon, G., Monboisse, J. C., and Kefalides, N. A. (1999) Cancer Res. 59, 4584-4590). In the present study we have examined the effect of CD47 and the integrin alpha(V)beta(3) on in vitro tumor cell chemotaxis and Ca(2+)(i) modulation in response to COL IV, from the anterior lens capsule (ALC-COL IV) and peptides from its NC-1 domain. COL IV as well as the alpha3(IV) peptide promoted tumor cell chemotaxis with an immediate increase in intracellular [Ca(2+)]. Treating tumor cells with CD47 and integrin alpha(V)beta(3)-reactive antibodies reduced chemotaxis as well as the rise in [Ca(2+)](i) in response to ALC-COL IV or the alpha3(IV)185-203 peptide but not to Engelbreth-Holm-Swarm-COL IV or fibronectin. The alpha3(IV)185-203 synthetic peptide stimulated an increase in calcium from intracellular stores exclusively, whereas ALC-COL IV, Engelbreth-Holm-Swarm-COL IV, and fibronectin stimulated Ca(2+) flux from both internal and external stores. Furthermore, treatment of the cells with Ca(2+) chelator bis-(O-aminophenoxyl)ethane-N,N,N',N'-tetraaceticacid- acetomethoxy ester inhibited chemotaxis toward both ALC-COL IV and the alpha3(IV)185-203 peptide. These data indicate that CD47 and integrin alpha(V)beta(3) regulate tumor cell chemotaxis in response to COL IV and the alpha3(IV)185-203 peptide through a Ca(2+)-dependent mechanism.

Amino Acid Sequence↗
PubMed2000

A specific sequence of the noncollagenous domain of the alpha3(IV) chain of type IV collagen inhibits expression and activation of matrix metalloproteinases by tumor cells.

The invasive properties of melanoma cells correlate with the expression of matrix metalloproteinases (MMPs) and their physiological modulators (tissue inhibitors of metalloproteinase and membrane-type MMPs) and with that of the alphaVbeta3 integrin. We investigated the effect of anterior lens capsule type IV collagen and of the alpha3(IV) collagen chain on the invasive properties of various tumor cell lines (HT-144 melanoma cells, HT-1080 fibrosarcoma cells). We demonstrated that anterior lens capsule type IV collagen or specifically the synthetic peptide alpha3(IV) 185-203 inhibited both the migration of melanoma or fibrosarcoma cells as well as the activation of membrane-bound MMP-2 by decreasing the expressions of MT1-MMP and the beta3 integrin subunit.

Amino Acid Sequence↗
PubMed2000

Preface

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Journal Article↗
PubMed2000

Contribution of the plasmin/matrix metalloproteinase cascade to the retraction of human fibroblast populated collagen lattices.

To assess the contribution of the plasmin/matrix metalloproteinase cascade in lattices retraction, human gingival fibroblast-populated collagen lattices were supplemented with plasminogen. The rate of lattice retraction was enhanced by addition of plasminogen. This effect was concomitant to plasmin generation, prostromelysin-1 and procollagenase activation. Plasminogen-mediated initiation of that proteolytic cascade was accompanied by conspicuous changes in cell morphology and collagen fibers organization. At day 1 of culture fibroblasts shifted from a rounded (control) to an elongated (in presence of plgn) shape. At the latest stage of retraction, intense vacuolization around fibroblasts was noticed in plgn-supplemented lattices which paralleled the increased collagen degradation. Plgn-enhancing influence on the initial phase of lattice retraction could be totally annihilated by either aprotinin or Batimastat. Those data emphasize the crucial importance of the plasmin-MMP proteolytic cascade in granulation tissue retraction in a healing wound.

Cells, Cultured↗
PubMed2000

Involvement of the ceramide signaling pathway in modulating the differentiated state of porcine thyroid cells.

Neutral sphingomyelinase (Smase) is a cell membrane-associated phospholipase that hydrolyzes sphingomyelin to phosphocholine and ceramide, a lipid second messenger involved in cell differentiation and/or apoptosis. We first evidenced that porcine cultured thyroid cells could express neutral Smase activity even if thyrotropin (TStH), an essential hormone in thyroid cell differentiation, was found to induce a 1.7-fold decrease in Smase activity. Triggering the ceramide pathway by exogenous addition of neutral bacterial Smase (0.1 U/mL for 48 h), which transiently increased ceramide level by fourfold, drastically modified thyroid cell morphology. The follicle-like structures generated by TSH were disrupted, and the Smase-induced cell spreading was accompanied by a parallel loss of cell ability to iodinate proteins as well as a decrease of the adenylate cyclase system response. These inhibitory effects have been reproduced using short-chain exogenous ceramide analogs (C2-ceramides). Overall these data showed that ceramides emerged as potential mediators of dedifferentiation in thyroid cells.

Animals↗
PubMed2000

A peptide of the alpha 3(IV) chain of type IV collagen modulates stimulated neutrophil function via activation of cAMP-dependent protein kinase and Ser/Thr protein phosphatase.

Previous reports from our laboratories showed that type IV collagen from anterior lens capsule (ALC) inhibited stimulated neutrophil function. This property was shown to reside in the region comprising residues 185-203 of the non-collagenous domain (NC1) of the alpha 3(IV) chain. We also reported that ALC-type IV collagen or the synthetic alpha 3(IV) 185-203 peptide, induced a rise in intracellular cAMP which persisted for up to 60 minutes. In the present work we extend our previous studies on signal transduction by alpha 3(IV) 185-203 and we provide new data showing the involvement of cAMP-dependent PKA and protein phosphatases. The data also show that the alpha 3(IV) peptide triggered a rise in intracellular calcium that was dependent on phospholipase C activation. Inhibitors of the Ca(2+)/calmodulin system suppressed both the alpha 3(IV) 185-203 peptide-induced cAMP increase and the inhibitory activity of the peptide on f-Met-Leu-Phe triggered O(2)(-) generation. When alpha 3(IV) 185-203 peptide-induced calcium mobilization was blocked by U-73122, an inhibitor of phospholipase C activation, or by BAPTA/AM, a chelator of intracellular calcium, the inhibitory effect of the peptide on PMA-triggered O(2)(-) production was also abolished. These findings provide evidence that signal transduction by the alpha 3(IV) peptide occurs via pathways which involve calcium. Indeed, the cAMP increase was shown to be mediated by adenosine and adenosine A2 receptors and required calcium elevation, since adenosine deaminase, theophilline, dimethylpropargylxanthine, trifluoperazine or autocamtide-2 related inhibitory peptide, suppressed the activity of the alpha 3(IV) peptide. The inhibitory effect of the peptide on f-Met-Leu-Phe-induced O(2)(-) generation was slightly affected by 1 microM KT5720 or H89, two inhibitors of cAMP-dependent PKA, but was completely suppressed by 10 nM calyculin A or 10 microM okadaic acid, two inhibitors of ser/thr phosphatases. These results suggest that Ser/Thr protein phosphatases and/or cAMP-dependent PKA are involved in signal transduction by the alpha 3(IV) 185-203 peptide and is consistent with the concept that adenosine receptor occupancy modulates neutrophil function.

Adenosine↗
PubMed2000

[Personal sports training in the management of obese boys aged 12 to 16 years].

OBJECTIVE: Estimation of both physical and psychological effects of an adapted physical training on children undergoing an obesity treatment. MATERIAL AND METHODS: The survey was carried out on 36 obese boys (ages = 12-16 years) who stayed in the medical center for at least four months. Eighteen of them were trained with the SELF method (the SELF-training is global, progressive, adapted to each boy, controlled and takes place within a ten-week period with five sessions a fortnight, each session lasting 30 to 40 minutes). The parameters that were studied concerned auxology, breathing function exploration, aerobic and anaerobic capacities, muscle strength and psychomotor qualities; the subjective effects of the training were estimated with a questionnaire about life quality, and the hand test. At inclusion the results were reported to a standard kind of population. At the end of the training the results of the 18 boys that were trained were compared to those of the 18 controls. RESULTS: Compared to a standard population, the obese children' aerobic capacity is diminished for the maximum power but is identical in absolute value for the VO2 max; their anaerobic capacities, muscle strength and psychomotor capacities are lower and their psyche is affected by the disease. After a three-month training period and after comparison with the 'control' group, there can be noticed a significant improvement in the psychomotor capacities, a major tendency for the improvement of the aerobic capacities and very positive effects on the psyche. CONCLUSION: SELF-training in association with dietetics appears to be very useful in the therapeutic care of obese children. For the follow-up at home it would need to be registered within the domain of physiotherapy.

Adolescent↗
PubMed2000

[Pulmonary cystic images as a presentation of a pleuropulmonary blastoma].

A five-month-old infant presented with a sudden choking cough and mild dyspnea. Bilateral cystic pulmonary images were found on a chest X-ray, leading to exploratory surgery. A pleuropulmonary blastoma, a rare malignant embryonic tumor of childhood, was diagnosed on histologic examination. This case illustrates the necessity of performing surgical resection and histologic evaluation of any pulmonary cystic malformations, particularly when bilateral.

Cysts↗
PubMed2000

Analysis of the ex vivo specificity of human gelatinases A and B towards skin collagen and elastic fibers by computerized morphometry.

Cutaneous aging and chronic exposure to UV irradiation leads to alterations in the appearance and biochemical composition of the skin. Members of the MMP family have been involved in the destruction of the extracellular matrix. Among them, gelatinases A and B were found to display elastolytic activity, in vitro. In this study, we first determined the ex vivo elastolytic potential of both endopeptidases, using human skin tissue sections and computerized morphometric analyses, and compared it with those of neutrophil elastase. In such conditions, gelatinase B (50 nM) induced 50% elastolysis. The percentage of elastic fibers degraded by gelatinase A (10-100 nM) never exceeded 10%. Elastolysis by gelatinase B and leukocyte elastase was characterized by a decrease in fiber length and an increase in the average diameter of the fibers. In addition, gelatinase B exhibited fibrillin-degrading activities. On the contrary, gelatinase A (50 nM) elicited up to 50% hydrolysis of collagen fibers, preferentially degrading type III collagen fibers. Gelatinase B did not promote any collagen degrading activity. Our data suggested that in vivo gelatinases could disrupt most extracellular matrix structures of human skin. Gelatinase B and to a much lesser extent, gelatinase A would degrade components of the elastic fibers network while gelatinase A, but not gelatinase B, would alter mostly collagen fibers and also degrade constituents of the dermo-epidermal junction.

Collagen↗
PubMed2000

Long-term outcome of idiopathic pulmonary hemosiderosis in children.

We retrospectively analyzed the long-term outcome of idiopathic pulmonary hemosiderosis (IPH) in 15 children. IPH started at a mean age of 5 years, and the mean duration of follow-up was 17.2 years (range, 10-36 yr). Four patients developed immune disorders, 3 cases of rheumatoid polyarthritis or rheumatoid polyarthritis-like diseases and 1 case of celiac disease. Respiratory outcome showed that 3 patients had severe symptoms: 2 patients developed severe pulmonary fibrosis resulting in major chronic respiratory insufficiency, and 1 patient had severe asthma. Twelve patients (80%) had mild or no respiratory problems and were able to lead a normal life. According to chest X-ray and pulmonary function test data, 4 patients had normal chest X-ray and no evidence of restrictive syndrome, 6 patients had an interstitial pattern on chest X-ray and evidence of restrictive pattern, 1 patient had an interstitial pattern but normal lung function, and 1 patient had a normal chest X-ray but evidence of mixed obstructive and restrictive pattern. Our results show that long-term survival is possible in patients with IPH. Factors of poor prognosis seem to be the presence of antineutrophil cytoplasm antibodies (ANCA) or other autoantibodies. No other clinical or biological predictive factors for prolonged survival were found.

Adolescent↗
PubMed2000

Bilateral cystic pleuropulmonary blastoma in early infancy.

We report 2 cases of multifocal cystic (type 1) pleuropulmonary blastoma, diagnosed during the first 6 months of life. This rare entity must be recognized before evolution into the prognostically unfavorable type 2 or type 3 pleuropulmonary blastoma.

Female↗
PubMed1999

Identification of CD47/integrin-associated protein and alpha(v)beta3 as two receptors for the alpha3(IV) chain of type IV collagen on tumor cells.

Previous studies from our laboratories demonstrated that a peptide from the noncollagenous domain of the alpha3 chain of basement membrane collagen (COL IV), comprising residues 185-203, inhibits polymorphonuclear leukocyte activation and melanoma cell proliferation independently of its ability to promote cell adhesion; these properties require the presence of the triplet -SNS- at residues 189-191 (J. C. Monboisse et al., J. Biol. Chem., 269: 25475-25482, 1994; J. Han et al., J. Biol. Chem., 272: 20395-20401, 1997). More recently, we demonstrated that native COL IV and -SNS-containing synthetic peptides (10 microg/ml) added to culture medium inhibit the proliferation of not only melanoma cells but also breast, pancreas, and stomach tumor cells up to 82% and prostate tumor cells by 15%. This inhibition was shown to be dependent on a COL IV- or peptide-induced increase in intracellular cAMP (T. A. Shahan et al., Connect. Tissue Res., 40: 221-232, 1999). Attempts to identify the putative receptor(s) on tumor cells led to the isolation of five proteins (Mr 33,000, 52,000, 72,000, 95,000, and 250,000) from melanoma and prostate cells by affinity purification with the alpha3(IV)179-208 peptide. The Mr 52,000, 95,000, and 250,000 proteins were shown to be CD47/integrin-associated protein(IAP), the integrin beta3 subunit, and the alpha(v)beta3 integrin complex, respectively. The Mr 33,000 and 72,000 proteins have not yet been identified. To confirm the specificity of ligand binding to the receptors, cell membranes from either melanoma or prostate tumor cells were pretreated with the unlabeled ligand alpha3(IV)187-191 (-YYSNS-); alternatively, the peptide was pretreated with a peptide-reactive monoclonal antibody (A5D7) before receptor isolation. These treatments inhibited the purification of CD47/IAP, the integrin beta3 subunit, and the alpha(v)beta3 integrin complex from tumor cells. Furthermore, cells treated with CD47/IAP- or the alpha(v)beta3 integrin-reactive antibodies prevented the alpha3(IV)185-203 peptide from inhibiting cell proliferation and the subsequent rise in intracellular cAMP. Pretreating cells with the alpha3(IV)187-191 (-YYSNS-) peptide also inhibited their adhesion to the alpha3(IV)185-203 peptide substrate, whereas the inactive alpha1(IV)185-203 peptide, from the same region of the alpha1 chain as the alpha3(IV)185-203 peptide, had no effect. Incubation of cells with either CD47/IAP and/or alpha(v)beta3 integrin-reactive antibodies inhibited their adhesion to the alpha3(IV)185-203 peptide, whereas antibodies to the beta1 and beta2 integrin subunits were without effect. These data suggest that ALC-COL IV, through its alpha3(IV) chain, inhibits tumor cell proliferation using the receptors CD47/IAP and the alpha(v)beta3 integrin.

Amino Acid Sequence↗
PubMed1999

A peptide of the alpha3 chain of type IV collagen protects basement membrane against damage by PMN.

We have shown that basement membrane (BM) collagen (type IV), and specifically the peptide CNYYSNSYSFWLASLNPER (a.a. 185-203), from the non-collagenous domain of the alpha3 chain inhibits PMN. We examined the role of this peptide on PMN damage to BM in a vessel wall model. The presence of the endothelial monolayer as well as treatment of PMN with the alpha3(IV) 185-203 peptide reduced damage to BM by non-activated but not by activated PMN. The damage inhibition is unique to the alpha3(IV) peptide and not exhibited by comparable alpha1(IV) and alpha2(IV) chain peptides. A shorter peptide alpha3(IV) 185-191, containing the -SNS- triplet, reduced damage, whereas the one lacking the triplet, residues 194-203, was not effective. The CD47-alphavbeta3 integrin complex is the receptor for the alpha3(IV) peptide. Incubation of PMN with CD47 reactive mAb followed by the alpha3(IV) peptide abolished its protective effect on BM damage.

Amino Acid Sequence↗