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眼刺激性物质暴露后人眼角膜上皮细胞的脂质组学分析突出了磷脂和鞘脂代谢物在去污剂毒性机制中的作用。

Lipidomic analysis of human corneal epithelial cells exposed to ocular irritants highlights the role of phospholipid and sphingolipid metabolisms in detergent toxicity mechanisms.

机构信息

Sorbonne Université UM80, INSERM UMR 968, CNRS UMR 7210, Institut de la Vision, IHU Foresight, Paris, France; UMR CNRS 8038 CiTCoM, Chimie Toxicologie Analytique et Cellulaire, Université de Paris, Faculté de Pharmacie, Paris, France.

UMR CNRS 8038 CiTCoM, Chimie Toxicologie Analytique et Cellulaire, Université de Paris, Faculté de Pharmacie, Paris, France.

出版信息

Biochimie. 2020 Nov;178:148-157. doi: 10.1016/j.biochi.2020.07.015. Epub 2020 Aug 3.

DOI:10.1016/j.biochi.2020.07.015
PMID:32758686
Abstract

Detergent chemicals, widely used in household products, in pharmaceutical, medical, cosmetic and industrial fields, have been linked to side effects and involved in several eye diseases. On the ocular surface, detergents can interfere with the corneal epithelium, the most superficial layer of the cornea, representing a line of defence against external aggression. Despite its major role in numerous biological functions, there is still little data regarding disruption of lipid homeostasis induced by ocular irritants. To this purpose, a lipidomic analysis using UPLC-HRMS/MS-ESI ± was performed on human corneal epithelial (HCE) cells incubated with three widely known ocular irritants: benzalkonium chloride (BAK), sodium lauryl sulfate (SLS) and Triton X-100 (TXT). We found that these ocular irritants lead to a profound modification of the HCE cell lipidome. Indeed, the cell content of ceramide species increased widely while plasmalogens containing polyunsaturated fatty acid species, especially docosahexaenoic acids, decreased. Furthermore, these irritants upregulated the activity of phospholipase A. The present study demonstrates that BAK, SLS and TXT induced disruption of the cell lipid homeostasis, highlighting that lipids mediate inflammatory and cell death processes induced by detergents in the cornea. Lipidomics may thus be regarded as a valuable tool to investigate new markers of corneal damage.

摘要

清洁剂化学物质广泛应用于家庭产品、制药、医疗、美容和工业领域,已被证实与副作用有关,并涉及多种眼部疾病。在眼表面,清洁剂会干扰角膜上皮(角膜的最浅层),这是抵御外部侵袭的第一道防线。尽管它在许多生物学功能中起着重要作用,但关于眼刺激物引起的脂质动态平衡破坏的数据仍然很少。为此,我们使用 UPLC-HRMS/MS-ESI(±)对用三种广泛使用的眼刺激物(苯扎氯铵(BAK)、十二烷基硫酸钠(SLS)和 Triton X-100(TXT))孵育的人角膜上皮(HCE)细胞进行了脂质组学分析。我们发现这些眼刺激物导致 HCE 细胞脂质组发生深刻变化。事实上,神经酰胺种类的细胞含量广泛增加,而含有多不饱和脂肪酸种类的脑苷脂,特别是二十二碳六烯酸,含量减少。此外,这些刺激物还上调了磷脂酶 A 的活性。本研究表明,BAK、SLS 和 TXT 诱导细胞脂质动态平衡破坏,这表明脂质介导了角膜中清洁剂引起的炎症和细胞死亡过程。因此,脂质组学可以被视为研究角膜损伤新标志物的有价值的工具。

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