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...
Ausführliche Beschreibung
Autor*in: |
Carmela Conte [verfasserIn] Samuela Cataldi [verfasserIn] Cataldo Arcuri [verfasserIn] Alessandra Mirarchi [verfasserIn] Andrea Lazzarini [verfasserIn] Mercedes Garcia-Gil [verfasserIn] Tommaso Beccari [verfasserIn] Francesco Curcio [verfasserIn] Elisabetta Albi [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: International Journal of Molecular Sciences - MDPI AG, 2003, 22(2021), 17, p 9287 |
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Übergeordnetes Werk: |
volume:22 ; year:2021 ; number:17, p 9287 |
Links: |
Link aufrufen |
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DOI / URN: |
10.3390/ijms22179287 |
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Katalog-ID: |
DOAJ049822950 |
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10.3390/ijms22179287 doi (DE-627)DOAJ049822950 (DE-599)DOAJfa4f9cb5b36a47dc89d0fe8061eaf58b DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Carmela Conte verfasserin aut Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. ceramide exosome sphingomyelin embryonic cell differentiation vitamin D Biology (General) Chemistry Samuela Cataldi verfasserin aut Cataldo Arcuri verfasserin aut Alessandra Mirarchi verfasserin aut Andrea Lazzarini verfasserin aut Mercedes Garcia-Gil verfasserin aut Tommaso Beccari verfasserin aut Francesco Curcio verfasserin aut Elisabetta Albi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 17, p 9287 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:17, p 9287 https://doi.org/10.3390/ijms22179287 kostenfrei https://doaj.org/article/fa4f9cb5b36a47dc89d0fe8061eaf58b kostenfrei https://www.mdpi.com/1422-0067/22/17/9287 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 17, p 9287 |
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10.3390/ijms22179287 doi (DE-627)DOAJ049822950 (DE-599)DOAJfa4f9cb5b36a47dc89d0fe8061eaf58b DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Carmela Conte verfasserin aut Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. ceramide exosome sphingomyelin embryonic cell differentiation vitamin D Biology (General) Chemistry Samuela Cataldi verfasserin aut Cataldo Arcuri verfasserin aut Alessandra Mirarchi verfasserin aut Andrea Lazzarini verfasserin aut Mercedes Garcia-Gil verfasserin aut Tommaso Beccari verfasserin aut Francesco Curcio verfasserin aut Elisabetta Albi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 17, p 9287 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:17, p 9287 https://doi.org/10.3390/ijms22179287 kostenfrei https://doaj.org/article/fa4f9cb5b36a47dc89d0fe8061eaf58b kostenfrei https://www.mdpi.com/1422-0067/22/17/9287 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 17, p 9287 |
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10.3390/ijms22179287 doi (DE-627)DOAJ049822950 (DE-599)DOAJfa4f9cb5b36a47dc89d0fe8061eaf58b DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Carmela Conte verfasserin aut Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. ceramide exosome sphingomyelin embryonic cell differentiation vitamin D Biology (General) Chemistry Samuela Cataldi verfasserin aut Cataldo Arcuri verfasserin aut Alessandra Mirarchi verfasserin aut Andrea Lazzarini verfasserin aut Mercedes Garcia-Gil verfasserin aut Tommaso Beccari verfasserin aut Francesco Curcio verfasserin aut Elisabetta Albi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 17, p 9287 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:17, p 9287 https://doi.org/10.3390/ijms22179287 kostenfrei https://doaj.org/article/fa4f9cb5b36a47dc89d0fe8061eaf58b kostenfrei https://www.mdpi.com/1422-0067/22/17/9287 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 17, p 9287 |
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10.3390/ijms22179287 doi (DE-627)DOAJ049822950 (DE-599)DOAJfa4f9cb5b36a47dc89d0fe8061eaf58b DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Carmela Conte verfasserin aut Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. ceramide exosome sphingomyelin embryonic cell differentiation vitamin D Biology (General) Chemistry Samuela Cataldi verfasserin aut Cataldo Arcuri verfasserin aut Alessandra Mirarchi verfasserin aut Andrea Lazzarini verfasserin aut Mercedes Garcia-Gil verfasserin aut Tommaso Beccari verfasserin aut Francesco Curcio verfasserin aut Elisabetta Albi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 17, p 9287 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:17, p 9287 https://doi.org/10.3390/ijms22179287 kostenfrei https://doaj.org/article/fa4f9cb5b36a47dc89d0fe8061eaf58b kostenfrei https://www.mdpi.com/1422-0067/22/17/9287 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 17, p 9287 |
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10.3390/ijms22179287 doi (DE-627)DOAJ049822950 (DE-599)DOAJfa4f9cb5b36a47dc89d0fe8061eaf58b DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Carmela Conte verfasserin aut Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. ceramide exosome sphingomyelin embryonic cell differentiation vitamin D Biology (General) Chemistry Samuela Cataldi verfasserin aut Cataldo Arcuri verfasserin aut Alessandra Mirarchi verfasserin aut Andrea Lazzarini verfasserin aut Mercedes Garcia-Gil verfasserin aut Tommaso Beccari verfasserin aut Francesco Curcio verfasserin aut Elisabetta Albi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 17, p 9287 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:17, p 9287 https://doi.org/10.3390/ijms22179287 kostenfrei https://doaj.org/article/fa4f9cb5b36a47dc89d0fe8061eaf58b kostenfrei https://www.mdpi.com/1422-0067/22/17/9287 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 17, p 9287 |
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2021-01-01T00:00:00Z |
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Carmela Conte misc QH301-705.5 misc QD1-999 misc ceramide misc exosome misc sphingomyelin misc embryonic cell differentiation misc vitamin D misc Biology (General) misc Chemistry Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells |
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Vitamin D3 Enriches Ceramide Content in Exosomes Released by Embryonic Hippocampal Cells |
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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. |
abstractGer |
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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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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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. 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