title: Alteration of proteomic profiles in PBMC isolated from patients with Fabry disease: preliminary findings.
abstract: Fabry disease (FD) is an X-linked progressive multisystem disease due to mutations in the gene encoding the lysosomal enzyme α-galactosidase A (α-GalA). The deficiency in α-GalA activity leads to an intra-lysosomal accumulation of neutral glycosphingolipids, mainly globotriaosylceramide (Gb3), in various organs and systems. Enzyme replacement therapy is available and alternative therapeutic approaches are being explored. No diagnostic test, other than sequencing of the α-galactosidase A gene, is available, no biomarker has been proven useful to screen for and predict the disease, and underlying mechanisms are still elusive. The aim of this study is to identify FD specific biomarkers and to better understand the pathophysiological changes that occur over time in FD. We compared peripheral blood mononuclear cells (PBMC) from FD patients (n = 8) with control PBMC from healthy individuals (n = 6), by two-dimensional electrophoresis (2DE) and the detected differentially expressed proteins were then subjected to matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). In FD patients we identified, among the down-regulated proteins, Calnexin, Rho GDP-dissociation inhibitor 2, Rho GDP-dissociation inhibitor 1, Chloride intracellular channel protein 1; on the other hand γ-enolase, 14-3-3 protein theta, 14-3-3 protein zeta/delta, and galectin-1 were identified as up-regulated proteins. Calnexin and Rho GDP-dissociation inhibitor-1,2 are related to protein folding, signal transduction and cell proliferation. This is the first time that γ-enolase and galectin-1 are described to be up-regulated in Fabry patients. Levels of γ-enolase increase dramatically in cardiovascular accidents and cerebral trauma, whereas galectins are regulators of acute and chronic inflammation. These findings may improve our understanding of the molecular mechanisms underlying the pathology and provide new insight and knowledge for future studies in this field.
authors: Laboratory of Proteomics, Institute of Biomedicine and Molecular Immunology (IBIM), CNR, Palermo, Italy.
authors: Diego
authors: D
authors: Cigna
authors: Claudia
authors: C
authors: D'Anna
authors: Carmela
authors: C
authors: Zizzo
authors: Daniele
authors: D
authors: Francofonte
authors: Iacopo
authors: I
authors: Sorrentino
authors: Paolo
authors: P
authors: Colomba
authors: Giuseppe
authors: G
authors: Albeggiani
authors: Alessandro
authors: A
authors: Armini
authors: Laura
authors: L
authors: Bianchi
authors: Luca
authors: L
authors: Bini
authors: Giovanni
authors: G
authors: Duro
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis; D000328:Adult; D015415:Biomarkers; D037281:Calnexin / Q000096:biosynthesis; D049109:Cell Proliferation; D018118:Chloride Channels / Q000096:biosynthesis; D015536:Down-Regulation; D000795:Fabry Disease / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D037483:Galectin 1 / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis; D017510:Protein Folding; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation; D000519:alpha-Galactosidase / Q000235:genetics; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000096:biosynthesis; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000096:biosynthesis
chemical_list: D048948:14-3-3 Proteins; D015415:Biomarkers; C501966:CLIC1 protein, human; D018118:Chloride Channels; D037483:Galectin 1; D020543:Proteome; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D037281:Calnexin; C576330:GLA protein, human; D000519:alpha-Galactosidase; D010751:Phosphopyruvate Hydratase