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

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; Quinlan, Roy A.

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 cholesterol rich 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 whole body 2 Gy irradiated mice. Although cholesterol levels do not change significantly, IR dose-dependent 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 hours 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.

Citation

Uwineza, A., Cummins, I., Jarrin, M., Kalligeraki, A. K., Barnard, S., Mol, M., …Quinlan, R. A. (2023). Identification and quantification of ionising radiation-induced oxysterol formation in membranes of lens fibre cells. Advances in Redox Research, 7, Article 100057. https://doi.org/10.1016/j.arres.2022.100057

• Journal Article Type: Article
• Acceptance Date: Dec 13, 2022
• Online Publication Date: Dec 14, 2022
• Publication Date: 2023-04
• Deposit Date: Dec 19, 2022
• Publicly Available Date: Dec 19, 2022
• Journal: Advances in Redox Research
• Print ISSN: 2667-1379
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Article Number: 100057
• DOI: https://doi.org/10.1016/j.arres.2022.100057
• Public URL: https://durham-repository.worktribe.com/output/1186698