Identification and quantification of ionising radiation-induced oxysterol formation in membranes of lens fibre cells

Abstract

Ionising radiation (IR) is a cause of lipid peroxidation, and epidemiological data have revealed a correlation between exposure to IR and the development of eye lens cataracts. Cataracts remain the leading cause of blindness around the world. The plasma membranes of lens fibre cells are one of the most cholesterolrich membranes in the human body, forming lipid rafts and contributing to the biophysical properties of lens fibre plasma membrane. Liquid chromatography followed by mass spectrometry was used to analyse bovine eye lens lipid membrane fractions after exposure to 5 and 50 Gy and eye lenses taken from wholebody 2 Gy-irradiated mice. Although cholesterol levels do not change significantly, IR dose-dependant formation of the oxysterols 7β-hydroxycholesterol, 7-ketocholesterol and 5, 6-epoxycholesterol in bovine lens nucleus membrane extracts was observed. Whole-body X-ray exposure (2 Gy) of 12-week old mice resulted in an increase in 7β-hydroxycholesterol and 7-ketocholesterol in their eye lenses. Their increase regressed over 24 h in the living lens cortex after IR exposure. This study also demonstrated that the IR-induced fold increase in oxysterols was greater in the mouse lens cortex than the nucleus. Further work is required to elucidate the mechanistic link(s) between oxysterols and IR-induced cataract, but these data evidence for the first time that IR exposure of mice results in oxysterol formation in their eye lenses.

Publication DOI: https://doi.org/10.1016/j.arres.2022.100057
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
Additional Information: © 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Funding: AU, SB, EA and RAQ are part of the LDLensRad project that has received funding from the Euratom research and training programme 2014-2018 in the framework of the CONCERT [grant agreement No 662287]. This publication reflects only the author's view. Responsibility for the information and views expressed therein lies entirely with the authors. The European Commission is not responsible for any use that may be made of the information it contains. HKID acknowledges the support from Kidney Research UK grant PDF3/2014. GA and MHAM acknowledge the support of the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement number 675132 (http://cordis.europa.eu/project/rcn/198275_en.html). The financial support of the National Eye Research Foundation (AAK; SAC014) and the EuroCellNet COST Action (CA15214) that provided STSM support to AU, RAQ and GA are also gratefully acknowledged.
Uncontrolled Keywords: Age-related cataract,Cataractogenic load,Cholesterol,Cholesterol oxidation,Eye lens,Free radicals,Ionising radiation ,Lipid rafts,Occupational exposure threshold,Oxysterol formation,Posterior subcapsular cataract,Smith-Lemli-Optiz syndrome,X-rays,Biochemistry, Genetics and Molecular Biology (miscellaneous)
Publication ISSN: 2667-1379
Last Modified: 24 May 2024 07:17
Date Deposited: 19 Dec 2022 12:26
Full Text Link:
Related URLs: https://www.sci ... 667137922000297 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2023-04
Published Online Date: 2022-12-14
Accepted Date: 2022-12-13
Authors: Uwineza, Alice
Cummins, Ian
Jarrin, Miguel
Kalligeraki, Alexia K.
Barnard, Stephen
Mol, Marco
Degani, Genny
Altomare, Alessandra A.
Aldini, Giancarlo
Schreurs, An
Balschun, Detlev
Ainsbury, Elizabeth A.
Dias, Irundika HK (ORCID Profile 0000-0002-6620-8221)
Quinlan, Roy A.

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