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Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells

The release of exosomes can lead to cell–cell communication. Nutrients such as vitamin D3 and sphingolipids have important roles in many cellular functions, including proliferation, differentiation, senescence, and cancer. However, the specific composition of sphingolipids in exosomes and their chan...

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Autores principales: Conte, Carmela, Cataldi, Samuela, Arcuri, Cataldo, Mirarchi, Alessandra, Lazzarini, Andrea, Garcia-Gil, Mercedes, Beccari, Tommaso, Curcio, Francesco, Albi, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430480/
https://www.ncbi.nlm.nih.gov/pubmed/34502192
http://dx.doi.org/10.3390/ijms22179287
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author Conte, Carmela
Cataldi, Samuela
Arcuri, Cataldo
Mirarchi, Alessandra
Lazzarini, Andrea
Garcia-Gil, Mercedes
Beccari, Tommaso
Curcio, Francesco
Albi, Elisabetta
author_facet Conte, Carmela
Cataldi, Samuela
Arcuri, Cataldo
Mirarchi, Alessandra
Lazzarini, Andrea
Garcia-Gil, Mercedes
Beccari, Tommaso
Curcio, Francesco
Albi, Elisabetta
author_sort Conte, Carmela
collection PubMed
description The release of exosomes can lead to cell–cell communication. Nutrients such as vitamin D3 and sphingolipids have important roles in many cellular functions, including proliferation, differentiation, senescence, and cancer. However, the specific composition of sphingolipids in exosomes and their changes induced by vitamin D3 treatment have not been elucidated. Here, we initially observed neutral sphingomyelinase and vitamin D receptors in exosomes released from HN9.10 embryonic hippocampal cells. Using ultrafast liquid chromatography tandem mass spectrometry, we showed that exosomes are rich in sphingomyelin species compared to whole cells. To interrogate the possible functions of vitamin D3, we established the optimal conditions of cell treatment and we analyzed exosome composition. Vitamin D3 was identified as responsible for the vitamin D receptor loss, for the increase in neutral sphingomyelinase content and sphingomyelin changes. As a consequence, the generation of ceramide upon vitamin D3 treatment was evident. Incubation of the cells with neutral sphingomyelinase, or the same concentration of ceramide produced in exosomes was necessary and sufficient to stimulate embryonic hippocampal cell differentiation, as vitamin D3. This is the first time that exosome ceramide is interrogated for mediate the effect of vitamin D3 in inducing cell differentiation.
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spelling pubmed-84304802021-09-11 Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells Conte, Carmela Cataldi, Samuela Arcuri, Cataldo Mirarchi, Alessandra Lazzarini, Andrea Garcia-Gil, Mercedes Beccari, Tommaso Curcio, Francesco Albi, Elisabetta Int J Mol Sci Article The release of exosomes can lead to cell–cell communication. Nutrients such as vitamin D3 and sphingolipids have important roles in many cellular functions, including proliferation, differentiation, senescence, and cancer. However, the specific composition of sphingolipids in exosomes and their changes induced by vitamin D3 treatment have not been elucidated. Here, we initially observed neutral sphingomyelinase and vitamin D receptors in exosomes released from HN9.10 embryonic hippocampal cells. Using ultrafast liquid chromatography tandem mass spectrometry, we showed that exosomes are rich in sphingomyelin species compared to whole cells. To interrogate the possible functions of vitamin D3, we established the optimal conditions of cell treatment and we analyzed exosome composition. Vitamin D3 was identified as responsible for the vitamin D receptor loss, for the increase in neutral sphingomyelinase content and sphingomyelin changes. As a consequence, the generation of ceramide upon vitamin D3 treatment was evident. Incubation of the cells with neutral sphingomyelinase, or the same concentration of ceramide produced in exosomes was necessary and sufficient to stimulate embryonic hippocampal cell differentiation, as vitamin D3. This is the first time that exosome ceramide is interrogated for mediate the effect of vitamin D3 in inducing cell differentiation. MDPI 2021-08-27 /pmc/articles/PMC8430480/ /pubmed/34502192 http://dx.doi.org/10.3390/ijms22179287 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Conte, Carmela
Cataldi, Samuela
Arcuri, Cataldo
Mirarchi, Alessandra
Lazzarini, Andrea
Garcia-Gil, Mercedes
Beccari, Tommaso
Curcio, Francesco
Albi, Elisabetta
Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells
title Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells
title_full Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells
title_fullStr Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells
title_full_unstemmed Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells
title_short Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells
title_sort vitamin d3 enriches ceramide content in exosomes released by embryonic hippocampal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430480/
https://www.ncbi.nlm.nih.gov/pubmed/34502192
http://dx.doi.org/10.3390/ijms22179287
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