Phosphatidylserine metabolism modification precedes manganese-induced apoptosis and phosphatidylserine exposure in PC12 cells

Ferrara, Giuseppina; Gambelunghe, Angela; Mozzi, Rita; Migliorati, Graziella; Muzi, Giacomo; Buratta, Sandra

doi:10.1016/j.neuro.2013.07.006

Cited by 6 publications

(7 citation statements)

References 44 publications

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“…In summary, it appears that PS and PE level in cell membranes could be influenced by common as well as specific metabolic pathways, and further investigations could assess the role of each of them in association with the apoptotic process. The decrease in PS level correlates well with our previous study demonstrating that the PS synthesis, evaluated by the incorporation of radioactive serine into PS, is inhibited in Mn-treated cells [32]. However, since oxidized phospholipids were not determined, we could not exclude that the detection of reduced PS levels were also due to an increase in phospholipid peroxidation, as Mn is known to induce oxidative stress [42,43,50].…”

Section: Discussionsupporting

confidence: 88%

“…In agreement with our previous demonstration [32], only 48 h exposure to MnCl 2 induced apoptosis (40 % annexin V positive/propidium iodide negative cells by flow cytometry analysis), whereas 24 h exposed cells did not show apoptotic hallmarks (data not shown). Major changes in phospholipid composition were observed after 48 h MnCl 2 treatment ( Fig.…”

Section: Lipid Composition Of Pc12 Cells Treated For 24 and 48 H Withsupporting

confidence: 93%

“…The possibility that changes in lipid composition could be associated to Mn-induced apoptosis was suggested by our previous study demonstrating that MnCl 2 not only induces apoptosis but also modifies PS metabolism in PC12 cells, as assayed by radiolabelling techniques [32]. In particular, we observed that effects on PS metabolism were present even under condition (24 h treatment) that does not allow to detect apoptosis.…”

Section: Discussionmentioning

confidence: 69%

“…As apoptotic model, we chose PC12 cells treated with MnCl 2 , as Mn is a dopaminergic neurotoxin and in a previous study we demonstrated that Mn induces apoptosis and influences PS metabolism in PC12 cells [32]. We used PC12 cells treated with 1 mM MnCl 2 for 48 h, whereas cell exposed for 24 h were used to evaluate early events leading to apoptosis [32]. Phospholipid composition was determined in both …”

Section: Introductionmentioning

confidence: 99%

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Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells

et al. 2015

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Lipid composition of membranes is fundamental to modulate signaling pathways relying on lipid metabolites and/or membrane proteins, thus resulting in the regulation of important cell processes such as apoptosis. In this case, membrane remodeling is an early event important for the activation of signaling leading to cell death and removal of apoptotic cells. In the present study, we analyzed phospholipid, cholesterol and fatty acid content during apoptosis induced by manganese in PC12 cells. Lipid analysis of whole cells and detergent-resistant membranes was carried out by HPLC/GC. Results showed that apoptosis is associated with changes in lipid composition detectable in whole cell extracts, namely cholesterol, phosphatidylserine and phosphatidylethanolamine decreases. Noteworthy, phosphatidylserine level reduction was detectable before to the detection of apoptosis, in correlation with our previous study carried out by radioactive labelling. By contrast, phosphatidylserine and phosphatidylethanolamine changes were not detected in detergent resistant membranes, which instead showed an altered composition in phosphatidylinositol, phosphatidylcholine and sphingomyelin in apoptotic cells.

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Section: Discussionsupporting

confidence: 88%

Section: Lipid Composition Of Pc12 Cells Treated For 24 and 48 H Withsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells

et al. 2015

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“…This cellular shift may contribute to the progression of pathological changes from steatosis to inflammation . Consistently, pathological events such apoptosis are shown to be associated with an increase in PE and PS …”

Section: Resultsmentioning

confidence: 99%

Compositional Changes Among Triglycerides and Phospholipids During FATP4 Sensitization with Palmitate Lead to ER Stress in Cultured Cells

Seeßle¹,

Liebisch

Schmitz

et al. 2019

Euro J Lipid Sci & Tech

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FATP4 expression is upregulated in acquired obesity and polymorphisms in the FATP4 gene are associated with increased blood triglycerides (TG). Since non‐alcoholic fatty liver disease (NAFLD) is a manifestation of obesity, it is of interest to understand how FATP4 upon fat overload mediates alterations of lipids that lead to pathogenesis of fatty liver. A model system with FATP4‐overexpressed (FATP4) and control Huh‐7 cell lines is used to determine FATP4 response to palmitate (Pal). By lipidomics methods, cellular phospholipids (PL), neutral lipids TG, free cholesterol (FC), and cholesterol esters (CE) as well as lipoprotein secretion are determined. Without Pal, FATP4 cells show a significant increase of TG, phosphatidylcholine (PC), and the release of TG‐rich and cholesterol‐rich low density lipoproteins. Pal‐treated FATP4 cells show an increase of all PL subclasses except for phosphatidylserine (PS), TG, FC, and CE. By analyses of ratios among PL subclasses and between PL and neutral lipids, it is determined that FATP4 in response to Pal causes sequentially fatty‐acid channeling with a shift from PC and phosphatidylinositol (PI) to neutral lipids and from neutral lipids to PS and phosphatidylethanolamine (PE). This response is concomitant with an activation of CAAT/enhancer binding homologous protein and MAP Kinase JNK. Thus, FATP4 overexpression in response to Pal leads to enhancement of neutral lipids which play a central role in fatty‐acid distribution from PC and PI to PE and PS that led to an alteration of ER and mitochondrial membranes and subsequent stress signalling. Practical Applications: Activation of fatty acids by fatty acid transport proteins (FATP) plays an important role in development of obesity and NAFLD. This work highlights functional role of FATP4 on fatty‐acid distribution among neutral lipids and phospholipids upon fat overload. These changes may contribute to stress signalling in the pathogenesis of NAFLD. Compositional shift among total PL subclasses and neutral lipids.

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Lipidomic approach towards deciphering anandamide effects in rat decidual cell

et al. 2015

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Altered phospholipid (PL) metabolism has been associated with pregnancy disorders. Moreover, lipid molecules such as endocannabinoids (eCBs) and prostaglandins (PGs) are important mediators of reproductive events. In humans, abnormal decidualization has been linked with unexplained infertility, miscarriage and endometrial pathologies. Anandamide (AEA), the major eCB, induces apoptosis in rat decidual cells. In this study, the PL profile of rat decidual cells was characterized by a Mass spectrometry (MS) based lipidomic approach. Furthermore, we analyzed a possible correlation between changes in PL of rat decidual cells' membrane and AEA-induced apoptosis. We found an increase in phosphatidylserine and a reduction of cardiolipin and phophatidylinositol relative contents. In addition, we observed an increase in the content of alkyl(alkenyl) acylPL, plasmalogens, and of long chain fatty acids especially with high degrees of unsaturation, as well as an increase in lipid hydroperoxides in treated cells. These findings provide novel insights on deregulation of lipid metabolism by anandamide, which may display further implications in decidualization process.

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Phosphatidylserine metabolism modification precedes manganese-induced apoptosis and phosphatidylserine exposure in PC12 cells

Cited by 6 publications

References 44 publications

Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells

Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells

Compositional Changes Among Triglycerides and Phospholipids During FATP4 Sensitization with Palmitate Lead to ER Stress in Cultured Cells

Lipidomic approach towards deciphering anandamide effects in rat decidual cell

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