Lee Bo Kyung, Jee Hye Jin, Jung Yi-Sook
College of Pharmacy, Ajou University, Suwon 16499, Korea.
Research Institute of Pharmaceutical Sciences and Technology, Ajou University, Suwon 16499, Korea.
Antioxidants (Basel). 2021 Oct 23;10(11):1671. doi: 10.3390/antiox10111671.
In platelets, oxidative stress reportedly increases platelet adhesion to vessels, thus promoting the vascular pathology of various neurodegenerative diseases, including Alzheimer's disease (AD). Recently, it has been shown that β-amyloid (Aβ) can increase oxidative stress in platelets; however, the underlying mechanism remains elusive. In the present study, we aimed to elucidate the signaling pathway of platelet adhesion induced by Aβ, the major form of circulating Aβ, through Western blotting, immunofluorescence confocal microscopy, and fluorescence-activated cell sorting analysis. Additionally, we examined whether rosmarinic acid (RA), a natural polyphenol antioxidant, can modulate these processes. Our results show that Aβ-induced platelet adhesion is mediated through NADPH oxidase/ROS/PKC-δ/integrin αβ signaling, and these signaling pathways are significantly inhibited by RA. Collectively, these results suggest that RA may have beneficial effects on platelet-associated vascular pathology in AD.
据报道,在血小板中,氧化应激会增加血小板与血管的黏附,从而促进包括阿尔茨海默病(AD)在内的各种神经退行性疾病的血管病变。最近有研究表明,β-淀粉样蛋白(Aβ)可增加血小板中的氧化应激;然而,其潜在机制仍不清楚。在本研究中,我们旨在通过蛋白质免疫印迹法、免疫荧光共聚焦显微镜和荧光激活细胞分选分析,阐明循环Aβ的主要形式Aβ诱导血小板黏附的信号通路。此外,我们还研究了天然多酚抗氧化剂迷迭香酸(RA)是否能调节这些过程。我们的结果表明,Aβ诱导的血小板黏附是通过NADPH氧化酶/活性氧/蛋白激酶C-δ/整合素αβ信号介导的,而这些信号通路受到RA的显著抑制。总的来说,这些结果表明RA可能对AD中与血小板相关的血管病变具有有益作用。