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Cholesterol metabolism and glaucoma: Modulation of Muller cell membrane organization by 24S-hydroxycholesterol.

Ségolène Gambert 1 Pierre Henry Gabrielle 2 Elodie A.Y. Masson 1 Elise Léger-Charnay 1 A Ferrerro 2 Anne Vannier 1 Clément Gendrault 1 Méline Lachot 1 Catherine Creuzot Garcher 2, 1 Alain Bron 2, 3 Stéphane Grégoire 3 Laurent Leclere 1 L Martine 1 Géraldine Lucchi 4 Caroline Truntzer 4 Delphine Pecqueur 4 Lionel Brétillon 1, 3
1 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
2 Service d'Ophtalmologie (CHU de Dijon)
3 OEil, nutrition et signalisation cellulaire [CSGA]
CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
4 CLIPP - Plate-forme Protéomique CLIPP - Clinical and Innovation Proteomic Platform [Dijon]
FEMTO-ST - Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174), ICMUB - Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon]
Abstract : Glaucoma is a progressive and irreversible blinding neuropathy that is characterized by the loss of retinal ganglion cells (RGCs). Muller Glial Cell (MGC) activation is induced in retinal gliosis. MGCs are the most numerous glial cells in the retina and one of their roles is to sustain cholesterol homeostasis. 24S-hydroxycholesterol (24S-OHC) is one of the form of cholesterol elimination from the retina and is overexpressed during glaucoma. The objective of this study was to determine whether 24S-OHC triggers MGC membrane dynamics involving lipid rafts and contributes to gliosis at early and late time points. A proteomic analysis was carried out by nanoLC-MS/MS in raft and non-raft fractions from MGCs after treatment with 24S-OHC (10μM). The expression of structural and functional proteins was further analyzed by Western-blotting, as well as the levels of GM3 ganglioside by LC-MS. Cholesterol, sphingomyelin, saturated fatty acids and ganglioside GM3 are enriched in the rafts fractions in MGCs. Caveolin-1, flotillin-1, connexin-30 and -43 are localized in the MGCs rafts. Proteins implicated in adhesion or oxidative stress pathways in raft fractions were up and down-regulated by the treatment. Our data showed that 24S-OHC induced early changes in protein distribution in raft microdomains; however, further studies are needed to better characterize the surrounded mechanisms.
Keywords : 24S-hydroxycholesterol Muller cells Raft microdomain
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01565083
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Soumis le : mercredi 19 juillet 2017 - 14:32:08
Dernière modification le : jeudi 13 janvier 2022 - 12:00:21

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UNIV-BOURGOGNE | CNRS | UNIV-FCOMTE | UNIV-BM | INRA | UNIV-BM-THESE | CSGA | FEMTO-ST | INRAE | ICMUB | INC-CNRS

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Ségolène Gambert, Pierre Henry Gabrielle, Elodie A.Y. Masson, Elise Léger-Charnay, A Ferrerro, et al.. Cholesterol metabolism and glaucoma: Modulation of Muller cell membrane organization by 24S-hydroxycholesterol.. Chemistry and Physics of Lipids, Elsevier, 2017, S0009-3084(17)30020-8 (Part B), pp.179-191. ⟨10.1016/j.chemphyslip.2017.05.007⟩. ⟨hal-01565083⟩

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