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.

Heme Oxygenase‐1 May Affect Cell Signalling via Modulation of Ganglioside Composition

“…Gangliosides are ubiquitously found in tissues and body fluid with the most abundant expression in the nervous system [ 35 ]. The expression levels of gangliosides undergo dramatic changes during various physiological and pathological conditions including cell death, proliferation, differentiation, development, and oncogenesis [ 36 – 38 ] as well as neurological diseases [ 39 , 40 ]. These effects are largely attributed to the changes in expression levels of ganglioside synthases (glycosyltransferases) [ 41 , 42 ].…”

The Role of Lipids in Parkinson’s Disease

“…It plays a role in neuronal survival and differentiation, and neurotransmitter release [279]. Plasma levels of PS 40:4 are decreased in PD patients [222], but higher levels of PS 36:1, PS 36:1, 36:2, and 38:3, or overall PS, have been found in parkin-mutant fibroblasts [280], frontal cortex [224], and primary visual cortex [225] of PD patients, respectively. This is in agreement with the increased PS synthase activity that has been observed in the SN of PD patients [271].…”

Automated analysis of lipid drug-response markers by combined fast and high-resolution whole cell MALDI mass spectrometry biotyping

“…Whereas applications of MALDI-TOF MS-based lipid/metabolite fingerprinting of mammalian cell extracts have been described in several fields including bioprocess engineering 10 , to date few studies describe MALDI-TOF MS lipid/metabolite fingerprinting of non-extracted mammalian cells. Notable examples include cardiolipin fingerprinting of leukocytes as a screening tool for Barth syndrome 11 , and lipid profiling for characterization of breast cancer cell lines or of human skin fibroblasts with Parkin mutations in Parkinson’s disease research 12 , 13 . In a single notable pharmacology-related study, both WC-MALDI MS protein and lipid fingerprints of benign prostatic hyperplasia as well as prostate cancer cells treated with a single concentration of the peptide anti-cancer drug Degarelix were compared 14 .…”