Metabolism and phospholipid assembly of polyunsaturated fatty acids in human bone marrow mesenchymal stromal cells

Tigistu-Sahle, Feven; Lampinen, Milla; Kilpinen, Lotta; Holopainen, Minna; Lehenkari, Petri; Käkelä, Reijo

doi:10.1194/jlr.m070680

Cited by 22 publications

(27 citation statements)

References 78 publications

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“…18:3n-3), given to the differentiating cells at an earlier phase, did not immediately give rise to 22:6n-3, which is likely owing to the required multistep synthetic pathway. Compared to the synthesis of 20:4n-6 from its precursor 18:2n-6, the metabolism of 22:6n-3 from 18:3n-3 requires two additional chain elongations and a desaturation in the ER followed by a peroxisomal chain-shortening step, the process thus requiring more time and being less efficient than the synthesis of 20:4n-6 ( Tigistu-Sahle et al, 2017 ). The HLCs, however, were able to produce some 22:6n-3 from its precursors, as can be seen from the rising levels of e.g.…”

Section: Discussionmentioning

confidence: 99%

Lipidomic profiling of patient-specific induced pluripotent stem cell-derived hepatocyte-like cells

Kiamehr

Viiri

Vihervaara

et al. 2017

Disease Models &Amp; Mechanisms

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Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs) offer an alternative model to primary human hepatocytes to study lipid aberrations. However, the detailed lipid profile of HLCs is yet unknown. In the current study, functional HLCs were differentiated from iPSCs generated from dermal fibroblasts of three individuals by a three-step protocol through the definitive endoderm (DE) stage. In parallel, detailed lipidomic analyses as well as gene expression profiling of a set of lipid-metabolism-related genes were performed during the entire differentiation process from iPSCs to HLCs. Additionally, fatty acid (FA) composition of the cell culture media at different stages was determined. Our results show that major alterations in the molecular species of lipids occurring during DE and early hepatic differentiation stages mainly mirror the quality and quantity of the FAs supplied in culture medium at each stage. Polyunsaturated phospholipids and sphingolipids with a very long FA were produced in the cells at a later stage of differentiation. This work uncovers the previously unknown lipid composition of iPSC-HLCs and its alterations during the differentiation in conjunction with the expression of key lipid-associated genes. Together with biochemical, functional and gene expression measurements, the lipidomic analyses allowed us to improve our understanding of the concerted influence of the exogenous metabolite supply and cellular biosynthesis essential for iPSC-HLC differentiation and function. Importantly, the study describes in detail a cell model that can be applied in exploring, for example, the lipid metabolism involved in the development of fatty liver disease or atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Lipidomic profiling of patient-specific induced pluripotent stem cell-derived hepatocyte-like cells

Kiamehr

Viiri

Vihervaara

et al. 2017

Disease Models &Amp; Mechanisms

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“…GPLs of the PLC, platelet, and EV samples were analyzed as reported previously (47). Briefly, total lipids were extracted using Folch extraction (48), and the samples, spiked with internal standards and supplemented with 1% NH4OH, were infused into electrospray ionization source of triple quadrupole mass spectrometer (MS) Agilent 6490 Triple Quad LC/MS with iFunnel technology (Agilent Technologies, Santa Clara, CA, USA) using a flow rate of 10 µL/min, ion source temperature of 250 °C, instrument collision energies of 5 -45 eV depending on the lipid class, and nitrogen as the nebulizing (20 psi) and the drying gas (11 μL/min at 250 °C).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Lipid mediators in platelet concentrate and extracellular vesicles: Molecular mechanisms from membrane glycerophospholipids to bioactive molecules

Valkonen

Holopainen

Colas

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Platelets are collected for transfusion to patients with different hematological disorders, and for logistical reasons, platelets are stored as concentrates. Despite the carefully controlled conditions, platelets become activated during storage, and platelet concentrates (PLCs) may cause adverse inflammatory reactions in the recipients. We studied by mass spectrometry the lipidomic changes during storage of the clinical PLCs, the platelets isolated from PLCs, and the extracellular vesicles (EVs) thereof. The release of EVs from platelets increased with the prolonged storage time. The molar percentages of arachidonic acid-containing species were increased during storage especially in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine classes of glycerophopholipids. The increase of these species in the membrane glycerophopholipid composition paralleled the production of both proinflammatory and proresolving lipid mediators (LMs) as the amount of the arachidonic acid-derived LMs such as thromboxane B 2 and prostaglandin E 2 also increased in time. Moreover, several monohydroxy pathway markers and functionally relevant proinflammatory and proresolving LMs were detected in the PLC and the EVs, and some of these clearly accumulated during storage. By Western blot, the key enzymes of these pathways were shown to be present in the platelets and in many cases also in the EVs. Since the EVs were enriched in the fatty acid precursors of LMs, harbored LM-producing enzymes, contained the related monohydroxy pathway markers, and also secreted the final LM products, the

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“…At every sampling time point, 2 × 1.5 ml volumes of raw milk (of samples M1, M2, and M3) were withdrawn and stored at -80°C until analyses. The phospholipid analysis work flow was performed essentially as described by Tigistu-Sahle et al (2017) . Aliquots of milk lipid extracts were evaporated and dissolved in chloroform/methanol (1:2 v/v), spiked with internal standards and supplemented with 1% NH 4 OH just prior to direct infusion of the sample solution, at a flow rate of 10 μl/min, into the ESI source of a triple quadrupole mass spectrometer (Agilent 6490 Triple Quad LC/MS with iFunnel technology, Agilent Technologies, Inc., Santa Clara, CA, United States).…”

Section: Methodsmentioning

confidence: 99%

Phospholipolysis Caused by Different Types of Bacterial Phospholipases During Cold Storage of Bovine Raw Milk Is Prevented by N2 Gas Flushing

et al. 2018

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Cold storage aims to preserve the quality and safety of raw milk from farms to dairies; unfortunately, low temperatures also promote the growth of psychrotrophic bacteria, some of which produce heat-stable enzymes that cause spoilage of milk or dairy products. Previously, N2 gas flushing of raw milk has demonstrated significant potential as a method to hinder bacterial growth at both laboratory and pilot plant scales. Using a mass spectrometry-based lipidomics approach, we examined the impact of cold storage [at 6°C for up to 7 days, the control condition (C)], on the relative amounts of major phospholipids (phosphatidylethanolamine/PE, phosphatidylcholine/PC, phosphatidylserine/PS, phosphatidylinositol/PI, and sphingomyelin/SM) in three bovine raw milk samples, and compared it to the condition that received additional N2 gas flushing (N). As expected, bacterial growth was hindered by the N2-based treatment (over 4 log-units lower at day 7) compared to the non-treated control condition. At the end of the cold storage period, the control condition (C7) revealed higher hydrolysis of PC, SM, PE, and PS (the major species reached 27.2, 26.7, 34.6, and 9.9 μM, respectively), compared to the N2-flushed samples (N7) (the major species reached 55.6, 35.9, 54.0, and 18.8 μM, respectively). C7 samples also exhibited a three-fold higher phosphatidic acid (PA) content (6.8 μM) and a five-fold higher content (17.3 μM) of lysophospholipids (LPE, LPC, LPS, and LPI) whereas both lysophospholipids and PA remained at their initial levels for 7 days in N7 samples. Taking into consideration the significant phospholipid losses in the controls, the lipid profiling results together with the microbiological data suggest a major role of phospholipase (PLase) C (PLC) in phospholipolysis during cold storage. However, the experimental data also indicate that bacterial sphingomyelinase C, together with PLases PLD and PLA contributed to the degradation of phospholipids present in raw milk as well, and potential contributions from PLB activity cannot be excluded. Altogether, this lipidomics study highlights the beneficial effects of N2 flushing treatment on the quality and safety of raw milk through its ability to effectively hinder phospholipolysis during cold storage.

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Metabolism and phospholipid assembly of polyunsaturated fatty acids in human bone marrow mesenchymal stromal cells

Cited by 22 publications

References 78 publications

Lipidomic profiling of patient-specific induced pluripotent stem cell-derived hepatocyte-like cells

Lipidomic profiling of patient-specific induced pluripotent stem cell-derived hepatocyte-like cells

Lipid mediators in platelet concentrate and extracellular vesicles: Molecular mechanisms from membrane glycerophospholipids to bioactive molecules

Phospholipolysis Caused by Different Types of Bacterial Phospholipases During Cold Storage of Bovine Raw Milk Is Prevented by N2 Gas Flushing

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