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Int. J. Mol. Sci. 2018, 19(11), 3515; https://doi.org/10.3390/ijms19113515

Oncogenic H-Ras Expression Induces Fatty Acid Profile Changes in Human Fibroblasts and Extracellular Vesicles

1
Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy
2
Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy
3
CEMIN-Center of Excellence for Innovative Nanostructured Material, 06123 Perugia, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 15 September 2018 / Revised: 20 October 2018 / Accepted: 5 November 2018 / Published: 8 November 2018
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2018)
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Abstract

Extracellular vesicles (EVs) are lipid bilayer surrounded particles that are considered an additional way to transmit signals outside the cell. Lipids have not only a structural role in the organization of EVs membrane bilayer, but they also represent a source of lipid mediators that may act on target cells. Senescent cells are characterized by a permanent arrest of cell proliferation, but they are still metabolically active and influence nearby tissue secreting specific signaling mediators, including those carried by EVs. Notably, cellular senescence is associated with increased EVs release. Here, we used gas chromatography coupled to mass spectrometry to investigate the total fatty acid content of EVs released by fibroblasts undergoing H-RasV12-induced senescence and their parental cells. We find that H-RasV12 fibroblasts show increased level of monounsaturated and decreased level of saturated fatty acids, as compared to control cells. These changes are associated with transcriptional up-regulation of specific fatty acid-metabolizing enzymes. The EVs released by both controls and senescent fibroblasts show a higher level of saturated and polyunsaturated species, as compared to parental cells. Considering that fibroblasts undergoing H-RasV12-induced senescence release a higher number of EVs, these findings indicate that senescent cells release via EVs a higher amount of fatty acids, and in particular of polyunsaturated and saturated fatty acids, as compared to control cells. View Full-Text
Keywords: extracellular vesicles; oncogene-induced senescence; H-Ras; fatty acids; desaturases; elongases; acyl-coenzyme A synthetases extracellular vesicles; oncogene-induced senescence; H-Ras; fatty acids; desaturases; elongases; acyl-coenzyme A synthetases
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Sagini, K.; Urbanelli, L.; Costanzi, E.; Mitro, N.; Caruso, D.; Emiliani, C.; Buratta, S. Oncogenic H-Ras Expression Induces Fatty Acid Profile Changes in Human Fibroblasts and Extracellular Vesicles. Int. J. Mol. Sci. 2018, 19, 3515.

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