Hocine Slimani

Université Paris 13 Nord, Île-de-France, France

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Publications (9)29.36 Total impact

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    ABSTRACT: In order to promote siRNA transfer in tumour cells, we used an original cationic lipid, synthesized in our laboratory, dimethyl-hydroxyethyl-aminopropane-carbamoyl-cholesterol (DMHAPC-Chol). Liposomes were prepared from this lipid and dioleoylphosphatidylethanolamine (DOPE) in equimolar proportion. Its transfecting capacity was evaluated using ELISA, cell cytometry, and RT-PCR in estimating the silencing effect of VEGF siRNA. This liposome efficiently delivered VEGF siRNA in two human cancer cell lines abundantly secreting VEGF, A431 and MDA-MB-231. Results showed that 50 nM of VEGF siRNA carried by DMHAPC-Chol/DOPE liposomes already silenced more than 90% of VEGF in these cells. A comparative study with two commercial carriers indicated that the inhibition induced by VEGF siRNA transported by cationic DMHAPC-Chol/DOPE liposomes was comparable to that induced by INTERFERin and better than lipofectamine 2000. Moreover, a transfection by a GFP plasmid followed by a GFP siRNA showed that DMHAPC-Chol/DOPE liposomes compared to lipofectamine were less efficient for plasmid but better for siRNA transport. Following one of our previous works concerning cell delivery of plasmid ( Percot et al., 2004 ), the main interest of results presented here resides in the double potential of DMHAPC-Chol/DOPE liposomes to deliver little-sized siRNA as well as large nucleic acids in cells.
    Journal of Drug Targeting 05/2012; 20(4):347-54. · 2.77 Impact Factor
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    ABSTRACT: In this paper, liposomes containing a lipopeptide bearing a ligand specifically recognized by neuropilin-1 (NRP-1) have been used to target a human breast cancer cell line overexpressing this receptor. The synthesis of this lipopeptide, C16-A7R, formed by the sequence of 7 amino acids ATWLPPR, linked to a palmitoyl fatty chain by an amide bond was described. After the characterisation of cationic liposomes formulated with the lipopeptide, the results obtained using various techniques showed that the lipopeptide-based liposomes were well accumulated in cells of the human breast cancer line MDA-MB-231 overexpressing NRP-1. Delivery of reporter genes expressing either beta-galactosidase (beta-gal) or green fluorescent protein (GFP) was selectively enhanced in these cells when compared with NRP-1-negative cells. In MDA-MB-231 cells, an increase by 250% in beta-gal activity was observed when delivered by lipopeptide-based liposomes compared to cationic liposomes alone.
    Journal of Drug Targeting 01/2007; 14(10):694-706. · 2.77 Impact Factor
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    ABSTRACT: Genuine article : 115XK - Langue : English - Type : Article // Source = 04007P %1 15/01/07 %2 49571 %3 %4 0 %7 %?
    Journal of Drug Targeting 01/2006; 14:694-706. · 2.77 Impact Factor
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    ABSTRACT: The stromal cell-derived factor-1 (SDF-1) is a CXC chemokine, which plays critical roles in migration, proliferation, and differentiation of leukocytes. SDF-1 is the only known ligand of CXCR4, the coreceptor of X4 HIV strains. We show that SDF-1 binds to high- and low-affinity sites on HeLa cells. Coimmunoprecipitation studies demonstrate that glycanated and oligomerized syndecan-4 but neither syndecan-1, syndecan-2, betaglycan, nor CD44 forms complexes with SDF-1 and CXCR4 on these cells as well as on primary lymphocytes or macrophages. Moreover, biotinylated SDF-1 directly binds in a glycosaminoglycans (GAGs)-dependent manner to electroblotted syndecan-4, and colocalization of SDF-1 with syndecan-4 was visualized by confocal microscopy. Glycosaminidases pretreatment of the HeLa cells or the macrophages decreases the binding of syndecan-4 to the complex formed by it and SDF-1. In addition, this treatment also decreases the binding of the chemokine to CXCR4 on the primary macrophages but not on the HeLa cells. Therefore GAGs-dependent binding of SDF-1 to the cells facilitates SDF-1 binding to CXCR4 on primary macrophages but not on HeLa cell line. Finally, an SDF-1-independent heteromeric complex between syndecan-4 and CXCR4 was visualized on HeLa cells by confocal microscopy as well as by electron microscopy. Moreover, syndecan-4 from lymphocytes, monocyte derived-macrophages, and HeLa cells coimmunoprecipitated with CXCR4. This syndecan-4/CXCR4 complex is likely a functional unit involved in SDF-1 binding. The role of these interactions in the pathophysiology of SDF-1 deserves further study.
    Glycobiology 05/2004; 14(4):311-23. · 3.54 Impact Factor
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    ABSTRACT: Interaction of RANTES with its membrane ligands or receptors transduces multiple intracellular signals. Whether RANTES uses proteoglycans (PGs) belonging to the syndecan family to attach to primary cells expressing RANTES G-protein-coupled receptors (GPCRs) was investigated. We demonstrate that RANTES specifically binds to high and low affinity binding sites on human monocyte-derived macrophages (MDM). We show by co-immunoprecipitation experiments that RANTES is associated on these cells with syndecan-1 and syndecan-4, but neither with syndecan-2 nor with betaglycan, in addition to CD44 and its GPCRs, CCR5 and CCR1. Glycosaminidases pre-treatment of the monocyte derived-macrophages strongly decreases the binding of RANTES to syndecan-1 and syndecan-4 and also to CCR5, and abolishes RANTES binding to CD44. This suggests that glycosaminoglycans (GAGs) are involved in RANTES binding to the PGs and that such bindings facilitate the subsequent interaction of RANTES with CCR5, on the MDM, characterized by low membrane expression of CCR5. The role of these interactions in the pathophysiology of RANTES deserves further study.
    Biochimica et Biophysica Acta 11/2003; 1617(1-2):80-8. · 4.66 Impact Factor
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    ABSTRACT: It is believed that proteoglycans influence biological properties of chemokines. We show that the CC chemokine RANTES binds not only to high-affinity binding sites on CCR5-positive HeLa cells but also to low-affinity binding sites on HeLa cells expressing or lacking RANTES G protein-coupled receptors. Coimmunoprecipitation studies demonstrate that RANTES forms complexes with glycanated syndecan (SD)-1 and -4, in addition to CCR5 on the CCR5-positive HeLa cells. Moreover, confocal microscopy analysis shows the colocalization of RANTES with SD-1 and -4. Glycosaminoglycans removal from the cells by glycosaminidases treatment prevented RANTES binding to SD-1 and -4 and decreased RANTES binding to CCR5 on the CCR5-positive HeLa cells. Removal of glycosaminoglycans by glycosaminidases treatment of the complexes, RANTES/SD-1/SD-4/+/-CCR5, immobilized on beads, reversed SD-1 and -4 bindings. Therefore, RANTES bindings to SD-1 and -4 depend on glycosaminoglycans and facilitate RANTES interaction with CCR5. Extracting plasma membrane cholesterol abolished the coimmunoprecipitation of SD-1 with RANTES, suggesting that rafts are involved in RANTES association to SD-1. Confocal microscopy analysis as well as coimmunoprecipitation experiments show a RANTES-independent heteromeric complex on the CCR5-positive HeLa cells, SD-1, SD-4, and CCR5. This complex is likely a functional unit in which proteoglycans may modulate RANTES binding to CCR5.
    Glycobiology 10/2003; 13(9):623-34. · 3.54 Impact Factor
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    ABSTRACT: We have reported previously that human alpha(1)-acid glycoprotein (AGP) inhibits the infection of human monocyte-derived macrophages (MDM) by R5 HIV-1, and that a disulphide-bridged peptide mimicking the clade B HIV-1 gp120 consensus V3 domain (V3Cs) binds specifically to CCR5 (the major co-receptor of R5 HIV strains) on these cells [Seddiki, Rabehi, Benjouad, Saffar, Ferriere, Gluckman and Gattegno (1997) Glycobiology 7, 1229-1236]. The present study demonstrates that AGP binds specifically to MDM at high- and low-affinity binding sites with K(d) values of 16 nM and 4.9 microM respectively. The fact that heat denaturation of AGP only partly inhibited this binding (43%) suggests that protein-protein interactions are involved, as well as AGP glycans which are resistant to heat denaturation. Mannan, but not dextran, is a significant inhibitor (52%) of this binding, and sequential exoglycosidase treatment of AGP, which exposes penultimate mannose residues, has a strong stimulatory effect ( approximately 2.8-fold). Therefore AGP glycans (probably mannose residues) are involved, at least partly, in the binding of AGP to MDM. In addition, AGP inhibits the binding of V3Cs and macrophage inflammatory protein-1beta (MIP-1beta) to MDM. The anti-CCR5 monoclonal antibody 2D7, specific for the second extracellular loop of CCR5, also inhibited AGP binding (67%), whereas anti-CCR5 antibodies specific for the C-terminus of CCR5 region had no effect. Native AGP, like V3Cs (but not heat-denatured AGP), binds to 46 and 33-36 kDa electroblotted AGP-bound MDM membrane ligands, characterized as CCR5 by their interactions with anti-CCR5 antibodies and with MIP-1beta. Therefore both AGP glycans and MDM CCR5 are involved in the binding of AGP to MDM. This suggests that the inhibitory effect of AGP on the infection of human primary macrophages by R5 HIV-1 may be related to specific binding of AGP to a macrophage membrane lectin or lectin-like component and to CCR5.
    Biochemical Journal 06/2001; 356(Pt 1):121-8. · 4.65 Impact Factor
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    ABSTRACT: We show that cell surface glycans, sialic acid and mannose-containing species, are involved beside glycosaminoglycans (GAGs), heparan sulfate and chondroitin sulfate in the binding of full length (1--68) RANTES not only to CCR5 positive human primary lymphocytes or macrophages but also to CCR5 negative monocytic U937 cells. Pretreating the cells with neuraminidase, heparitinase, chondroitinase or adding soluble glycans such as mannan or GAGs (heparin or chondroitin sulfate), significantly inhibited RANTES binding. Such effects were not observed with truncated (10--68) RANTES. Heat-denaturation of (1--68) RANTES strongly decreased its binding to the cells, demonstrating involvement of the three-dimensional structure. Accordingly, full length, but not truncated (10--68) RANTES, specifically bound to soluble mannan as well as to mannose-divinylsulfone-agarose affinity matrix and to soluble heparin or chondroitin sulfate as well as to heparin-agarose. Soluble heparin exerts, depending on its concentration, inhibitory or enhancing effects on RANTES binding to mannose-divinylsulfone-agarose, which indicates that RANTES interaction with glycans is modulated by GAGs. These data demonstrate that full length RANTES, but not its (10--68) truncated counterpart, interacts with glycans and GAGs, in soluble forms or presented either by affinity matrices or CCR5 positive as well as CCR5 negative cells.
    Biochimica et Biophysica Acta 03/2001; 1510(1-2):354-66. · 4.66 Impact Factor
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