1. The role of the SIRT1/NF-κB/NLRP3 pathway in the pyroptosis of lens epithelial cells under shortwave blue light radiation.
- Author
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Ji Z, Zhang D, Wang Y, Liu X, Wang M, Zhu X, Yu Y, Tian J, Cai J, Chen Y, Dong M, and Li Z
- Subjects
- Animals, Humans, Rats, Blotting, Western, Blue Light adverse effects, Cells, Cultured, Disease Models, Animal, Oxidative Stress, Rats, Sprague-Dawley, Signal Transduction physiology, Cataract metabolism, Cataract pathology, Cataract etiology, Epithelial Cells metabolism, Epithelial Cells radiation effects, Lens, Crystalline radiation effects, Lens, Crystalline metabolism, NF-kappa B metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Pyroptosis physiology, Pyroptosis radiation effects, Sirtuin 1 metabolism
- Abstract
Cataracts are the world's number one blinding eye disease. Cataracts can only be effectively treated surgically, although there is a chance of surgical complications. One of the pathogenic processes of cataracts is oxidative stress, which closely correlated with pyroptosis. SIRT1 is essential for the regulation of pyroptosis. Nevertheless, the role of SIRT1 in formation of cataracts is unclear. In this work, we developed an in vitro model of shortwave blue light (SWBL)-induced scotomization in human lens epithelial cells (HLECs) and an in vivo model of SWBL-induced cataracts in rats. The study aimed to understand how the SIRT1/NF-κB/NLRP3 pathway functions. Additionally, the evaluation included cell death and the release of lactate dehydrogenase (LDH), a cytotoxicity marker, from injured cells. First, we discovered that SWBL exposure resulted in lens clouding in Sprague- Dawley (SD) rats and that the degree of clouding was positively linked to the duration of irradiation. Second, we discovered that SIRT1 exhibited antioxidant properties and was connected to the NF-κB/NLRP3 pathway. SWBL irradiation inhibited SIRT1 expression, exacerbated oxidative stress, and promoted nuclear translocation of NF-κB and the activation of the NLRP3 inflammasome, which caused LEC pyroptosis and ultimately led to cataract formation. Transient transfection to increase the expression of SIRT1 decreased the protein expression levels of NF-κB, NLRP3, caspase-1, and GSDMD, inhibited HLEC pyroptosis, and reduced the release of LDH, providing a potential method for cataract prevention and treatment., Competing Interests: Declaration of competing interest There are no declared competing interests for the writers., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
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