Peimin Lin, Jie Xu, Fan Yang, Dan Li, Rong Zhang, Yongxiang Jiang, Tianyu Zheng
{"title":"Elevated concentrations of amyloid-β oligomers and their proapoptotic effects on age-related cataract","authors":"Peimin Lin, Jie Xu, Fan Yang, Dan Li, Rong Zhang, Yongxiang Jiang, Tianyu Zheng","doi":"10.1096/fj.202301281RR","DOIUrl":null,"url":null,"abstract":"<p>Recently, amyloid-β oligomers (AβOs) have been studied as the primary pathogenic substances in Alzheimer's disease (AD). Our previous study revealed that the Aβ expression level is closely related to ARC progression. Here, we demonstrated that the accumulation of AβOs in the lens epithelium of age-related cataract (ARC) patients increased during ARC progression and that this alteration was consistent with the changes in mitochondrial function, oxidative stress, and cellular apoptosis. In vitro, human lens epithelial cells (HLECs) treated with AβOs exhibited Ca<sup>2+</sup> dyshomeostasis, impaired mitochondrial function, elevated oxidative stress levels, and increased apoptosis. Moreover, the proapoptotic effect of AβOs was alleviated after the uptake of mitochondrial Ca<sup>2+</sup> was inhibited. These results establish that AβOs may promote HLEC apoptosis by inducing mitochondrial Ca<sup>2+</sup> overload, thus preliminarily revealing the possible association between the accumulation of AβOs and other pathological processes in ARC.</p>","PeriodicalId":50455,"journal":{"name":"FASEB Journal","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FASEB Journal","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1096/fj.202301281RR","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Recently, amyloid-β oligomers (AβOs) have been studied as the primary pathogenic substances in Alzheimer's disease (AD). Our previous study revealed that the Aβ expression level is closely related to ARC progression. Here, we demonstrated that the accumulation of AβOs in the lens epithelium of age-related cataract (ARC) patients increased during ARC progression and that this alteration was consistent with the changes in mitochondrial function, oxidative stress, and cellular apoptosis. In vitro, human lens epithelial cells (HLECs) treated with AβOs exhibited Ca2+ dyshomeostasis, impaired mitochondrial function, elevated oxidative stress levels, and increased apoptosis. Moreover, the proapoptotic effect of AβOs was alleviated after the uptake of mitochondrial Ca2+ was inhibited. These results establish that AβOs may promote HLEC apoptosis by inducing mitochondrial Ca2+ overload, thus preliminarily revealing the possible association between the accumulation of AβOs and other pathological processes in ARC.
期刊介绍:
The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.