Chercheur

    Alexey V. Pshezhetsky , Ph.D.

    alexei.pchejetski@umontreal.ca
    Alexey V. Pshezhetsky
    Axe de recherche
    Santé métabolique et maladies complexes
    Thème de recherche
    Maladies génétiques et métaboliques au Québec : diagnostics, mécanismes et interventions
    Adresse
    CHUSJ - Centre de Recherche

    Téléphone
    514 345-4931 #2736

    Fax
    514 345-4766

    Titres

    • Professeur titulaire, Département de pédiatrie, Université de Montréal, 2006.
    • Professeur affilié, Département d'anatomie et de biologie cellulaire, Université McGill, 2005.
    • Professeur affilié, Département de biochimie, Université de Montréal, 1998.

    Formation

    • Postdoctorat en sciences médicales, Academy of Medical Sciences, Moscou, Russie, 1990.
    • PhD en biochimie, Moscow State University, Russie, 1988.
    • Maîtrise en biochimie, Moscow State University, Russie, 1985.

    Intérêts de recherche

    Biologie lysosomale et maladies de surcharge lysosomale

    Les lysosomes sont des organelles cytoplasmiques qui hébergent plus de 100 enzymes hydrolytiques impliquées dans la dégradation de la quasi-totalité des macromolécules biologiques. Toute défaillance dans la biogenèse, le ciblage lysosomal, l’organisation supramoléculaire ou la fonction d'un ou de plusieurs enzymes lysosomales peut conduire à la progression des maladies métaboliques, appelées maladies de surcharge lysosomale. Celles-ci sont causées par l'accumulation massive des substrats non dégradés des enzymes déficients dans les lysosomes des tissus affectés. Notre recherche vise à découvrir les gènes mutés dans les maladies lysosomales, l'identification des défauts moléculaires et biochimiques chez les patients et le développement de thérapies avec un accent particulier sur les maladies causées par les carences en sialidases lysosomales (sialidose, galactosialidose) et en
    N-acétyltransférases (mucopolysaccharidose IIIC).

    Acides sialiques et sialidases dans la signalisation de la cellule

    Les acides sialiques sont abondamment exprimés sur la surface de la cellule et impliqués dans la médiation de la reconnaissance entre les cellules, entre les cellules et la matrice extracellulaire ainsi qu’entre les cellules et une gamme de pathogènes, de bactéries et de protozoaires au cours de la réaction inflammatoire et immunitaire. Nous savons encore peu de choses sur le rôle de la sialidase (également appelée neuraminidase) et de la sialotransférase, qui peuvent régulariser l’affinité cellulaire en modifiant la sialylation des molécules de surface cellulaire. Par l’utilisation du modèle de souris génétiquement ciblée, nous étudions le rôle de la neuraminidase 1 (Neu1) en signalisation au cours de la réponse immunitaire, de la phagocytose, de l'absorption de glucose, ainsi que le rôle de la neuraminidase 4 (Neu4) dans le développement du cerveau.

    Sérines carboxypeptidases dans la régulation de la vasoconstriction et l’élastogénèse

    Les courts peptides vasoactifs sont reconnus comme de puissants régulateurs de la circulation du sang. Grâce à leur interaction avec les différents récepteurs de surface cellulaire, ces peptides peuvent moduler la pression artérielle par divers mécanismes tels que les contractions des muscles lisses vasculaires, l'augmentation ou la diminution du volume plasmatique et l’induction ou la suppression de remodelage de la paroi vasculaire. Par conséquent, les protéases impliquées dans le catabolisme des peptides vasoactifs, qui régularisent leur longévité fonctionnelle et la disponibilité, jouent un rôle important dans la régulation de la résistance vasculaire. À l’aide d’un modèle de souris knock-out, nous étudions le contribution de sérine carboxypeptidase lysosomale (cathepsine A) dans le traitement post-traductionnelle des peptides vasoactifs, y compris l'angiotensine et l'endothéline.

    Protéomique fonctionnelle et phosphoprotéomique

    La phosphorylation est la plus fréquente et importante des modifications post-traductionnelles des protéines. Malgré des recherches intensives consacrées au développement de méthodes pour l'analyse d'un phosphoprotéome, l'identification de phosphoprotéines cellulaires de faible abondance reste un défi, ce qui souligne la nécessité de mettre au point de nouvelles techniques. Notre équipe est impliquée dans le développement de nouvelles technologies visant l'analyse globale et l'analyse quantitative d’un phosphoprotéome, fondées sur les résines d'affinité pour l'isolement de phosphopeptides, de phosphoprotéines et de peptides marqués par isotopes. Ces technologies devraient permettre de comparer de phosphoprotéomes dans le but d'identifier de nouvelles cibles de médicaments à travers les voies de signalisation pharmaceutiques et métaboliques correspondantes.

    Prix et distinctions

    • Chercheur national, Fonds de la recherche en santé du Québec (FRSQ), avril 2002.
    • Prix d'excellence pédiatrique, Fondation des étoiles, novembre 2001.
    • Chercheur senior, FRSQ, avril 1999.
    • Chercheur junior 2, FRSQ, juin 1997.

Publications

Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1 - Pan X, Grigoryeva L, Seyrantepe V, Peng J, Kollmann K, Tremblay J, Lavoie JL, Hinek A, Lübke T, Pshezhetsky AV. Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in regulation of vasoconstriction via inactivation of endothelin-1. PLoS Genet 2014; 10(2): e1004146.

Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3K? pathway - Gayral S, Garnotel R, Castaing-Berthou A, Blaise S, Fougerat A, Berge E, Montheil A, Malet N, Wymann MP, Maurice P, Debelle L, Martiny L, Martinez LO, Pshezhetsky AV, Duca L, Laffargue M. Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3Kγ pathway. Cardiovasc Res 2014; 102(1): 118-127.

Desialylation of surface receptors as a new dimension in cell signaling - Pshezhetsky AV, Ashmarina L. Desialylation of surface receptors as a new dimension in cell signaling. Biochemistry (Mosc) 2013; 78(7): 736-745.

Positive regulation of insulin signaling by neuraminidase 1 - Dridi L, Seyrantepe V, Fougerat A, Pan X, Bonneil E, Thibault P, Moreau A, Mitchell GA, Heveker N, Cairo CW, Issad T, Hinek A, Pshezhetsky AV. Positive regulation of insulin signaling by neuraminidase 1. Diabetes 2013; 62(7): 2338-2346.

Identification of selective inhibitors for human neuraminidase isoenzymes using C4,C7-modified 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) analogues - Zhang Y, Albohy A, Zou Y, Smutova V, Pshezhetsky AV, Cairo CW. Identification of selective inhibitors for human neuraminidase isoenzymes using C4,C7-modified 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) analogues. J Med Chem 2013; 56(7): 2948-2958.

Global analysis of protein phosphorylation networks in insulin signaling by sequential enrichment of phosphoproteins and phosphopeptides - Fediaev M, Parmar A, Xu Y, Vyetrogon K, Difalco MR, Ashmarina L, Nifantiev I, Posner BI, Pshezhetsky AV. Global analysis of protein phosphorylation networks in insulin signaling by sequential enrichment of phosphoproteins and phosphopeptides. Mol BioSyst 2012; 8(5): 1461-1471.

Multidimensional proteomics for the identification of endothelial post mortem signals of importance in vascular remodeling - Sirois I, Pshezhetsky AV, Hébert MJ. Multidimensional proteomics for the identification of endothelial post mortem signals of importance in vascular remodeling. Dans: Man T-K, Flores RJ (eds). Proteomics - Human Diseases and Protein Functions. In Tech, 2012; 275-290.

Metabolism of vertebrate amino sugars with N-glycolyl groups: resistance of a2-8-linked N-glycolylneuraminic acid to enzymatic cleavage - Davies LR, Pearce OM, Tessier MB, Assar S, Smutova V, Pajunen M, Sumida M, Sato C, Kitajima K, Finne J, Gagneux P, Pshezhetsky AV, Woods R, Varki A. Metabolism of vertebrate amino sugars with N-glycolyl groups: resistance of α2-8-linked N-glycolylneuraminic acid to enzymatic cleavage. J Biol Chem 2012; 287(34): 28917-28931.

Caspase activation regulates the extracellular export of autophagic vacuoles - Sirois I, Groleau J, Pallet N, Brassard N, Hamelin K, Londono I, Pshezhetsky AV, Bendayan M, Hébert MJ. Caspase activation regulates the extracellular export of autophagic vacuoles. Autophagy 2012; 8(6): 927-937.

Hyaluronidase 1 and ß-hexosaminidase have redundant functions in hyaluronan and chondroitin sulfate degradation - Gushulak L, Hemming R, Martin D, Seyrantepe V, Pshezhetsky AV, Triggs-Raine B. Hyaluronidase 1 and β-hexosaminidase have redundant functions in hyaluronan and chondroitin sulfate degradation. J Biol Chem 2012; 287(20): 16689-16697.

Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors - Pshezhetsky AV, Hinek A. Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors. Glycoconj J 2011; 28(7): 441-452.

Spectral optical coherence tomography in a patient with type I sialidosis - Michalewska Z, Gajos A, Michalewski J, Nawrocki J, Pshezhetsky AV, Bogucki A. Spectral optical coherence tomography in a patient with type I sialidosis. Med Sci Monit 2011; 17(10): CS129-131.

Caspase-3-dependent export of TCTP: a novel pathway for antiapoptotic intercellular communication - Sirois I, Raymond MA, Brassard N, Cailhier J-F, Fediaev M, Hamelin K, Londono I, Bendayan M, Pshezhetsky AV, Hébert MJ. Caspase-3-dependent export of TCTP: a novel pathway for antiapoptotic intercellular communication. Cell Death Differ 2011; 18(3): 549-562.

Mice doubly-deficient in lysosomal hexosaminidase A and neuraminidase 4 show epileptic crises and rapid neuronal loss - Seyrantepe V, Lema P, Caqueret A, Dridi L, Bel Hadj S, Carpentier S, Boucher F, Levade T, Carmant L, Gravel R, Hamel E, Vachon P, Di Cristo G, Michaud JL, Morales C, Pshezhetsky AV. Mice doubly-deficient in lysosomal hexosaminidase A and neuraminidase 4 show epileptic crises and rapid neuronal loss. PLoS Genet 2010; 6(9): pii: e1001118.

Analysis of the biogenesis of heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase provides insights into the mechanism underlying its complete deficiency in mucopolysaccharidosis IIIC - Durand S, Feldhammer M, Bonneil E, Thibault P, Pshezhetsky AV. Analysis of the biogenesis of heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase provides insights into the mechanism underlying its complete deficiency in mucopolysaccharidosis IIIC. J Biol Chem 2010; 285(41): 31233-31242.

Epidermal growth factor and perlecan fragments produced by apoptotic endothelial cells co-ordinately activate ERK1/2-dependent antiapoptotic pathways in mesenchymal stem cells - Soulez M, Sirois I, Brassard N, Raymond MA, Nicodème F, Noiseux N, Durocher Y, Pshezhetsky AV, Hébert MJ. Epidermal growth factor and perlecan fragments produced by apoptotic endothelial cells co-ordinately activate ERK1/2-dependent antiapoptotic pathways in mesenchymal stem cells. Stem Cells 2010; 28(4): 810-820.

Regulation of phagocytosis in macrophages by the neuraminidase 1 - Seyrantepe V, Iannello A, Liang F, Kanshin E, Jayanth P, Samarani S, Szewczuk MR, Ahmad A, Pshezhetsky AV. Regulation of phagocytosis in macrophages by the neuraminidase 1. J Biol Chem 2010; 285(1): 206-215.

Desialylation of insulin receptors and IGF-1 receptors by Neuraminidase 1 controls the net proliferative response of L6 myoblasts to insulin - Arabkhari M, Bunda S, Wang Y, Wang A, Pshezhetsky AV, Hinek A. Desialylation of insulin receptors and IGF-1 receptors by Neuraminidase 1 controls the net proliferative response of L6 myoblasts to insulin. Glycobiology 2010; 20(5): 603-616.

Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling - Amith SR, Jayanth P, Franchuk S, Findlay S, Seyrantepe V, Beyaert R, Pshezhetsky AV, Szewczuk MR. Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. Cell Signal 2010; 22(2): 314-324.

Caspase-3-mediated secretion of connective tissue growth factor by apoptotic endothelial cells promotes fibrosis - Laplante P, Sirois I, Raymond MA, Kokta V, Béliveau A, Prat A, Pshezhetsky AV, Hébert MJ. Caspase-3-mediated secretion of connective tissue growth factor by apoptotic endothelial cells promotes fibrosis. Cell Death Differ 2010; 17(2): 291-303.

Serine carboxypeptidases in regulation of vasoconstriction and elastogenesis - Pshezhetsky AV, Hinek A. Serine carboxypeptidases in regulation of vasoconstriction and elastogenesis. Trends Cardiovasc Med 2009; 19(1): 11-17.

Analysis of protein phosphorylation by mass-spectrometry - Kanshin E, Nifantiev I, Pshezhetsky AV. Analysis of protein phosphorylation by mass-spectrometry. Mass Spectrometry 2009; 6(2): 103-120.

Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene - Feldhammer M, Durand S, Mrazova L, Boucher RM, Laframboise R, Steinfeld R, Wraith JE, Michelakakis H, van Diggelen O, Hrebicek M, Kmoch S, Pshezhetsky AV. Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene. Hum Mutat 2009; 30(6): 918-295.

The stoichiometry of protein phosphorylation in adipocyte lipid droplets: analysis by N-terminal isotope tagging and enzymatic dephosphorylation - Kanshin E, Wang S, Ashmarina L, Fediaev M, Nifantiev I, Mitchell GA, Pshezhetsky AV. The stoichiometry of protein phosphorylation in adipocyte lipid droplets: analysis by N-terminal isotope tagging and enzymatic dephosphorylation. Proteomics 2009; 9(22): 5067-5077.

Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C - Feldhammer M, Durand S, Pshezhetsky AV. Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C. PLoS ONE 2009; 4(10): e7434 (on line).

Dependence of pathogen molecule-induced toll-like receptor activation and cell function on Neu1 sialidase - Amith SR, Jayanth P, Franchuk S, Siddiqui S, Seyrantepe V, Gee K, Basta S, Beyaert R, Pshezhetsky AV, Szewczuk MR. Dependence of pathogen molecule-induced toll-like receptor activation and cell function on Neu1 sialidase. Glycoconj J 2009; 26(9): 1197-1212.

Enzymatic activity of lysosomal carboxypeptidase (cathepsin) a is required for proper elastic fiber formation and inactivation of endothelin-1 - Seyrantepe V, Hinek A, Peng J, Fediaev M, Ernest S, Kadota Y, Canuel M, Itoh K, Morales C, Lavoie J, Tremblay J, Pshezhetsky AV. Enzymatic activity of lysosomal carboxypeptidase (cathepsin) a is required for proper elastic fiber formation and inactivation of endothelin-1. Circulation 2008; 117(15): 1973-1981.

Lysosomal carboxypeptidase A - Pshezhetsky AV. Lysosomal carboxypeptidase A. Dans: Barrett AJ, Rawlings ND, Woessner JF (eds). Handbook of Proteolytic Enzymes, 2nd edition. Londres. Academic Press, 2008; (sous presse).

Caspase-3 activation triggers extracellular cathepsin L release and endorepellin proteolysis - Cailhier J-F, Sirois I, Raymond MA, Lepage S, Laplante P, Brassard N, Prat A, Iozzo RV, Pshezhetsky AV, Hébert MJ. Caspase-3 activation triggers extracellular cathepsin L release and endorepellin proteolysis. J Biol Chem 2008; 283(40): 27220-27229.

New affinity resin for phosphopeptide enrichment and subsequent mass-spectrometry analysis - Kanshin E, Nifantiev I, Pshezhetsky AV. New affinity resin for phosphopeptide enrichment and subsequent mass-spectrometry analysis. Mass Spectrometry 2008; 5(3): 195-202.

Mice deficient in Neu4 sialidase exhibit abnormal ganglioside catabolism and lysosomal storage - Seyrantepe V, Canuel M, Carpentier S, Landry K, Durand S, Feng L, Zeng J, Caqueret A, Gravel R, Marchesini S, Zwingmann C, Michaud JL, Morales C, Levade T, Pshezhetsky AV. Mice deficient in Neu4 sialidase exhibit abnormal ganglioside catabolism and lysosomal storage. Hum Mol Genet 2008; 17(11): 1556-1568.

Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands - Ruijter GJ, Valstar MJ, van de Kamp J, van der Helm RM, Durand S, van Diggelen O, Wevers RA, Poorthuis B, Pshezhetsky AV, Wijburg FA. Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands. Mol Genet Metab 2008; 93(2): 104-111.

Development of a novel noncompetitive antagonist of IL-1 receptor - Quiniou C, Sapieha P, Lahaie I, Hou X, Brault S, Beauchamp M, Leduc M, Rihakova L, Joyal JS, Nadeau S, Heveker N, Lubell W, Sennlaub F, Gobeil F, Miller G, Pshezhetsky AV, Chemtob S. Development of a novel noncompetitive antagonist of IL-1 receptor. J Immunol 2008; 180(10): 6977-6987.

Subcellular proteomics of cell differententiation: Quantitative analysis of the plasma membrane protein of Caco-2 cells - Pshezhetsky AV, Fediaev M, Ashmarina L, Mazur A, Budman L, Sinnett D, Labuda D, Beaulieu J-F, Ménard D, Nifantiev I, Levy E. Subcellular proteomics of cell differententiation: Quantitative analysis of the plasma membrane protein of Caco-2 cells. Proteomics 2007; 7(13): 2201-2215.

Proteomic analysis of vascular smooth muscle cells treated with ouabain - Pshezhetsky AV. Proteomic analysis of vascular smooth muscle cells treated with ouabain. Dans: Vivanco F (ed). Cardiovascular proteomics, methods and protocols. USA. Humana Press, 2007; 253-269.

Quantitative analysis of a proteome by N-terminal stable-isotope labelling of tryptic peptides - Fediaev M, Trudel S, Tjon-A-Pan N, Parmar A, Posner BI, Levy E, Nifantiev I, Pshezhetsky AV. Quantitative analysis of a proteome by N-terminal stable-isotope labelling of tryptic peptides. Rapid Commun Mass Spectrom 2007; 21(16): 2671-2679.

A genome-wide association study identifies novel risk loci for type 2 diabetes - Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 2007; 445(7130): 881-885.

Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway - Bifsha P, Landry K, Ashmarina L, Durand S, Seyrantepe V, Trudel S, Quiniou C, Chemtob S, Xu Y, Gravel R, Sladek R, Pshezhetsky AV. Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway. Cell Death Differ 2007; 14(3): 511-523.

Quantitative analysis of proteins using stable isotope matrix-purifyable labels (SIMPL) - Fediaev M, Nifantiev I, Pshezhetsky AV. Quantitative analysis of proteins using stable isotope matrix-purifyable labels (SIMPL). Mass Spectrometry 2007; 4(3): 218-222.

Mutations in TMEM76 Cause Mucopolysaccharidosis IIIC (Sanfilippo C Syndrome) - Hrebicek M, Mrazova L, Seyrantepe V, Durand S, Roslin NM, Noskova L, Hartmannova H, Ivanek R, Cizkova A, Poupetova H, Sikora J, Urinovska J, Stranecky V, Zeman J, Lepage P, Roquis D, Verner A, Ausseil J, Beesley CE, Maire I, Poorthuis B, van de Kamp J, van Diggelen O, Wevers RA, Hudson TJ, Fujiwara TM, Majewski J, Morgan K, Smoch S, Pshezhetsky AV. Mutations in TMEM76 Cause Mucopolysaccharidosis IIIC (Sanfilippo C Syndrome). Am J Hum Genet 2006; 79(5): 807-819.

Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly - Hinek A, Pshezhetsky AV, von Itzstein M, Starcher B. Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. J Biol Chem 2006; 281(6): 3698-3710.

An acetylated 120-kDa lysosomal transmembrane protein is absent from mucopolysaccharidosis IIIC fibroblasts: A candidate molecule for MPS IIIC - Ausseil J, Landry K, Seyrantepe V, Trudel S, Mazur A, Lapointe F, Pshezhetsky AV. An acetylated 120-kDa lysosomal transmembrane protein is absent from mucopolysaccharidosis IIIC fibroblasts: A candidate molecule for MPS IIIC. Mol Genet Metab 2006; 87(1): 22-31.

Dominant role for calpain in thromboxane-induced neuromicrovascular endothelial cytotoxicity - Quiniou C, Sennlaub F, Beauchamp M, Checchin D, Lahaie I, Brault S, Gobeil F, Sirinyan M, Kooli A, Hardy P, Pshezhetsky AV, Chemtob S. Dominant role for calpain in thromboxane-induced neuromicrovascular endothelial cytotoxicity. J Pharmacol Exp Ther 2006; 316(2): 618-627.

Monocyte differentiation upregulates the expression of the lysosomal sialidase, neu1 and triggers its targeting to the plasma membrane via MHC class II-positive compartments - Liang F, Seyrantepe V, Landry K, Ahmad R, Ahmad A, Stamatos NM, Pshezhetsky AV. Monocyte differentiation upregulates the expression of the lysosomal sialidase, neu1 and triggers its targeting to the plasma membrane via MHC class II-positive compartments. J Biol Chem 2006; 281(37): 27526-27538.

Gene expression profiles of normal proliferative and differentiating human intestinal epithelial cells: a comparison with the Caco-2 cell model - Tremblay E, Auclair J, Delvin EE, Levy E, Ménard D, Pshezhetsky AV, Rivard N, Seidman EG, Sinnett D, Vachon PH, Beaulieu J-F. Gene expression profiles of normal proliferative and differentiating human intestinal epithelial cells: a comparison with the Caco-2 cell model. J Cell Biochem 2006; 99(4) : 1175-1186.

The microcell-mediated transfer of human chromosome 8 restores the deficient N-acetyltransferase activity in skin fibroblasts of mucopolysaccharidosis type IIIC patients - Seyrantepe V, Tihy F, Pshezhetsky AV. The microcell-mediated transfer of human chromosome 8 restores the deficient N-acetyltransferase activity in skin fibroblasts of mucopolysaccharidosis type IIIC patients. Hum Genet 2006; 120(2): 293-296.

Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages - Stamatos NM, Liang F, Cross AS, Wang L-X, Pshezhetsky AV. Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages. FEBS Lett 2005; 272(10): 2545-2556.

Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor - Raymond MA, Désormeaux A, Labelle A, Soulez M, Soulez G, Langelier Y, Pshezhetsky AV, Hébert MJ. Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor. Biochem Biophys Res Commun 2005; 338(3): 1374-1382.

Apoptosis of endothelial cells triggers a caspase-dependent anti-apoptotic paracrine loop active on VSMC - Raymond MA, Désormeaux A, Laplante P, Vigneault N, Filep JG, Landry K, Pshezhetsky AV, Hébert MJ. Apoptosis of endothelial cells triggers a caspase-dependent anti-apoptotic paracrine loop active on VSMC. FASEB J 2004; 18(6): 705-707.

Lysosomal carboxypeptidase - Pshezhetsky AV. Lysosomal carboxypeptidase. Dans: Barrett AJ, Rawlings ND, Woessner JF (eds). Handbook of Proteolytic Enzymes, 2nd edition. Londres. Academic Press, 2004; XX.

Apoptosis in serum-deprived vascular smooth muscle cells; evidence for cell volume-independent mechanism - Orlov SN, Pchejetski DV, Taurin S, Thorin-Trescases N, Maximov GV, Pshezhetsky AV, Rubin CM, Hamel P. Apoptosis in serum-deprived vascular smooth muscle cells; evidence for cell volume-independent mechanism. Apoptosis 2004; 9(1): 55-66.

Neu4, a novel human lysosomal lumen sialidase confers normal phenotype to sialidosis cells - Seyrantepe V, Landry K, Trudel S, Hassan JA, Morales C, Pshezhetsky AV. Neu4, a novel human lysosomal lumen sialidase confers normal phenotype to sialidosis cells. J Biol Chem 2004; 279(35): 37021-37029.

Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase - Soni K, Lehner R, Metalnikov P, O'Donnell P, Semache M, Gao W, Ashman K, Pshezhetsky AV, Mitchell GA. Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase. J Biol Chem 2004; 279(39): 40683-40689.

Localisation of a gene for mucopolysaccharidosis IIIC to the pericentromeric region of chromosome 8 - Ausseil J, Loredo-Osti JC, Verner A, Darmond-Zwaig C, Maire I, Poorthuis B, van Diggelen O, Hudson TJ, Fujiwara TM, Morgan K, Pshezhetsky AV. Localisation of a gene for mucopolysaccharidosis IIIC to the pericentromeric region of chromosome 8. J Med Genet 2004; 41(12): 941-945.

Clinical variability of type II sialidosis by C808T mutation - Rodriguez-Criado G, Pshezhetsky AV, Rodriguez-Becerra A, Gomez de Terreros I. Clinical variability of type II sialidosis by C808T mutation. Am J Med Genet 2003; 116A(4): 368-371.

Inhibition of Na(+),K(+)(i)-ATPase by ouabain triggers epithelial cell death independently of the inversion of the [Na+](i)/[K+](i) ratio - Pchejetski DV, Taurin S, Der Sarkissian S, Lopina OD, Pshezhetsky AV, Tremblay J, deBlois D, Hamet P, Orlov SN. Inhibition of Na(+),K(+)(i)-ATPase by ouabain triggers epithelial cell death independently of the inversion of the [Na+](i)/[K+](i) ratio. Biochem Biophys Res Commun 2003; 301(3): 735-744.

Molecular pathology of NEU-1 in sialidosis - Seyrantepe V, Poupetova H, Froissart R, Zabot M-T, Maire I, Pshezhetsky AV. Molecular pathology of NEU-1 in sialidosis. Hum Mutat 2003; 22(5): 343-352.

[3H]-thymidine labeling of DNA triggers apoptosis potentiated by E1A-adenoviral protein - Orlov SN, Pchejetski DV, Der Sarkissian S, Adarichev V, Taurin S, Pshezhetsky AV, Tremblay J, Maximov GV, deBlois D, Bennett MR, Hamel P. [3H]-thymidine labeling of DNA triggers apoptosis potentiated by E1A-adenoviral protein. Apoptosis 2003; 8(2): 199-208.

Proteome analysis and functional expression identify mortalin as an antiapoptotic gene induced by elevation of [Na+]i/[K+]i ratio in cultured vascular smooth muscle cells - Taurin S, Seyrantepe V, Orlov SN, Tremblay T-L, Thibault P, Bennett MR, Hamel P, Pshezhetsky AV. Proteome analysis and functional expression identify mortalin as an antiapoptotic gene induced by elevation of [Na+]i/[K+]i ratio in cultured vascular smooth muscle cells. Circ Res 2002; 91(10): 915-922.

Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes - Itoh K, Naganawa Y, Matsuzawa F, Aikawa S, Doi H, Sasagasako N, Yamada T, Kira J, Kobayashi T, Pshezhetsky AV, Sakuraba H. Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes. J Hum Genet 2002; 47(1): 29-37.

Suppression of programmed cell death by intracellular cAMP is not mediated by expression of genes encoding an inhibitor of apoptosis - Taurin S, Ryazhsky GG, Maximova NV, Chuchalin AG, Hamet P, Pshezhetsky AV, Orlov SN. Suppression of programmed cell death by intracellular cAMP is not mediated by expression of genes encoding an inhibitor of apoptosis. Biochemistry 2002; 67(2): 254-259.

Lysosomal multienzyme complex: Biochemistry, genetics and molecular pathophysiology - Pshezhetsky AV, Ashmarina L. Lysosomal multienzyme complex: Biochemistry, genetics and molecular pathophysiology. Dans: Moldave K (ed). Progress in Nucleic Acid Research and Molecular Biology, vol 69. Californie. Academic Press, 2001; 81-114.

Clinical presentation of congenital sialidosis in a patient with a neuraminidase gene frameshift mutation - Bucholz T, Molitor G, Lukong KE, Praun M, Genzel-Boroviczény O, Freund M, Pshezhetsky AV, Schulz PA. Clinical presentation of congenital sialidosis in a patient with a neuraminidase gene frameshift mutation. Eur J Pediatr 2001; 160: 26-30.

Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex - Lukong KE, Landry K, Elsliger M-A, Chang Y, Lefrançois S, Morales C, Pshezhetsky AV. Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex. J Biol Chem 2001; 276: 17286-17290.

Antiproliferative effect of brief exposure to cholera toxin in vascular smooth muscle cells: role of cAMP and protein kinase - Thorin-Trescases N, Orlov SN, Taurin S, Dulin NO, Allen BG, deBlois D, Tremblay J, Pshezhetsky AV, Hamet P. Antiproliferative effect of brief exposure to cholera toxin in vascular smooth muscle cells: role of cAMP and protein kinase. Can J Physiol Pharmacol 2001; 79: 471-480.

Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail - Lukong KE, Seyrantepe V, Landry K, Trudel S, Ahmad A, Gahl WA, Lefrançois S, Morales C, Pshezhetsky AV. Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail. J Biol Chem 2001; 276: 46172-46181.

Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex - Lukong KE, Elsliger M-A, Chang Y, Richard C, Thomas G, Carey W, Tylki-Szymanska A, Czartoryska B, Bucholz T, Criado G, Palmeri S, Pshezhetsky AV. Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex. Hum Mol Genet 2000; 9(7): 1075-1085.

Molecular and structural studies of Japanese patients with sialidosis type 1 - Naganawa Y, Itoh K, Shimmoto M, Takiguchi K, Doi H, Nishizawa Y, Kobayashi T, Kamei S, Lukong KE, Pshezhetsky AV, Sakuraba H. Molecular and structural studies of Japanese patients with sialidosis type 1. J Hum Genet 2000; 45: 241-249.

3-Hydroxy-3-methylglutaryl coenzyme A lyase: processing and half-lives in peroxisomes and mitochondria - Ashmarina L, Pshezhetsky AV, Mitchell GA. 3-Hydroxy-3-methylglutaryl coenzyme A lyase: processing and half-lives in peroxisomes and mitochondria. J Lipid Res 1999; 40: 70-75.

Identification of UDP-N-acetylglucosamine-phosphotransferase binding sites on lysosomal protease, cathepsins A, B and D - Lukong KE, Elsliger M-A, Potier M, Pshezhetsky AV. Identification of UDP-N-acetylglucosamine-phosphotransferase binding sites on lysosomal protease, cathepsins A, B and D. Biochemistry 1999; 38: 73-80.

Purification, cDNA cloning and expression of gp56 - a new human blood plasma peptidase homologous to NAALADase/prostate-specific membrane antigene - Gingras F, Richard C, El-Alfy MV, Morales C, Potier M, Pshezhetsky AV. Purification, cDNA cloning and expression of gp56 - a new human blood plasma peptidase homologous to NAALADase/prostate-specific membrane antigene. J Biol Chem 1999; 274: 11742-11750.

Lysosomal carboxypeptidase A - Pshezhetsky AV. Lysosomal carboxypeptidase A. Dans: Barrett AJ, Rawlings ND, Woessner JF (eds). Handbook of Proteolytic Enzymes. Londres. Academic Press, 1998; 393-398.

Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves it's rapid degradation - Vinogradova M, Michaud L, Mezentsev A, Lukong KE, El-Alfy MV, Morales C, Potier M, Pshezhetsky AV. Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves it's rapid degradation. Biochem J 1998; 330: 641-650.

Cloning of mouse lysosomal sialidase and its expression in mouse and human sialidase-deficient fibroblasts - Igdoura S, Gafuik C, Mertineit C, Saberi F, Pshezhetsky AV, Potier M, Trasler C, Gravel R. Cloning of mouse lysosomal sialidase and its expression in mouse and human sialidase-deficient fibroblasts. Hum Mol Genet 1998; 7: 115-121.

Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A/protective protein gene - Richard C, Tranchemontagne J, Elsliger M-A, Mitchell GA, Potier M, Pshezhetsky AV. Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A/protective protein gene. Hum Mutat 1998; 11: 461-469.

Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis - Pshezhetsky AV, Richard C, Michaud L, Igdoura S, Wang S, Elsliger M-A, Qu J, Leclerc D, Gravel R, Dallaire L, Potier M. Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis. Nat Genet 1997; 15: 316-320.

Leaning disability in rats induced by the immunosuppression of Cathepsin A in blood plasma - Ashmarin IP, Buzinova E, Vinogradova M, Potier M, Pshezhetsky AV. Leaning disability in rats induced by the immunosuppression of Cathepsin A in blood plasma. Neurosci Res Commun 1997; 21: 153-162.

Association of N-acetyl-galactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of b-galactosidase, cathepsin A and alpha-neuraminidase: possible implication for intralysosomal catabolism of keratan sulfate - Pshezhetsky AV, Potier M. Association of N-acetyl-galactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of b-galactosidase, cathepsin A and alpha-neuraminidase: possible implication for intralysosomal catabolism of keratan sulfate. J Biol Chem 1996; 271: 28359-28365.

Comparative modeling of substrate binding in the S1' subsite of serine carboxypeptidases from yeast, wheat and human - Elsliger M-A, Pshezhetsky AV, Vinogradova MV, Svedas V, Potier M. Comparative modeling of substrate binding in the S1' subsite of serine carboxypeptidases from yeast, wheat and human. Biochemistry 1996; 35: 14899-14909.

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