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Pyrogallol intermediates elicit beta-amyloid secretion via radical formation and alterations in intracellular trafficking, distinct from pyrogallol-generated superoxide
Redox Biology ( IF 10.7 ) Pub Date : 2024-05-24 , DOI: 10.1016/j.redox.2024.103180
Bong-Geum Jang 1 , Boyoung Choi 1 , Min-Ju Kim 2
Affiliation  

This study unveils a novel role of pyrogallol (PG), a recognized superoxide generator, in inducing beta-amyloid (Aβ) secretion in an Alzheimer's disease (AD) cellular model. Contrary to expectations, the analysis of dihydroethidium fluorescence and UV-VIS spectrum scanning reveals that Aβ secretion arises from PG reaction intermediates rather than superoxide or other by-products. Investigation into Aβ secretion mechanisms identifies dynasore-dependent endocytosis and BFA-dependent exocytosis as independent pathways, regulated by tiron, tempol, and superoxide dismutase. Cell-type specificity is observed, with 293sw cells showing both pathways, while H4sw cells and primary astrocytes from an AD animal model exclusively exhibit the Aβ exocytosis pathway. This exploration contributes to understanding PG's chemical reactions and provides insights into the interplay between environmental factors, free radicals, and AD, linking occupational PG exposure to AD risk as reported in the literature.

中文翻译:


邻苯三酚中间体通过自由基形成和细胞内运输的改变引起β-淀粉样蛋白分泌,这与邻苯三酚产生的超氧化物不同



这项研究揭示了连苯三酚 (PG)(一种公认的超氧化物生成剂)在诱导阿尔茨海默病 (AD) 细胞模型中 β-淀粉样蛋白 (Aβ) 分泌方面的新作用。与预期相反,二氢乙锭荧光和UV-VIS光谱扫描分析表明Aβ分泌来自PG反应中间体而不是超氧化物或其他副产物。对 Aβ 分泌机制的研究发现,dynasore 依赖性内吞作用和 BFA 依赖性胞吐作用是独立的途径,受 tiron、tempol 和超氧化物歧化酶调节。观察到细胞类型特异性,293sw 细胞显示这两种途径,而来自 AD 动物模型的 H4sw 细胞和原代星形胶质细胞只显示 Aβ 胞吐作用途径。这一探索有助于理解 PG 的化学反应,并深入了解环境因素、自由基和 AD 之间的相互作用,将职业性 PG 暴露与文献报道的 AD 风险联系起来。
更新日期:2024-05-24
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