title: Lipid profiling of parkin-mutant human skin fibroblasts.
abstract: Parkin mutations are a major cause of early-onset Parkinson's disease (PD). The impairment of protein quality control system together with defects in mitochondria and autophagy process are consequences of the lack of parkin, which leads to neurodegeneration. Little is known about the role of lipids in these alterations of cell functions. In the present study, parkin-mutant human skin primary fibroblasts have been considered as cellular model of PD to investigate on possible lipid alterations associated with the lack of parkin protein. Dermal fibroblasts were obtained from two unrelated PD patients with different parkin mutations and their lipid compositions were compared with that of two control fibroblasts. The lipid extracts of fibroblasts have been analyzed by combined matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) and thin-layer chromatography (TLC). In parallel, we have performed direct MALDI-TOF/MS lipid analyses of intact fibroblasts by skipping lipid extraction steps. Results show that the proportions of some phospholipids and glycosphingolipids were altered in the lipid profiles of parkin-mutant fibroblasts. The detected higher level of gangliosides, phosphatidylinositol, and phosphatidylserine could be linked to dysfunction of autophagy and mitochondrial turnover; in addition, the lysophosphatidylcholine increase could represent the marker of neuroinflammatory state, a well-known component of PD.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari "A. Moro", Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Lobasso
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari "A. Moro", Bari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tanzarella
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Vergara
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Maffia
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari "A. Moro", Bari, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cocco
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari "A. Moro", Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Corcelli
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism*; D061251:Primary Cell Culture; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D015415:Biomarkers; D006028:Glycosphingolipids; D010743:Phospholipids; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: MALDI-TOF/MS; fibroblasts; gangliosides; lipidomics; phospholipids