Ambient particulate matter triggers defective autophagy and hijacks endothelial cell renewal through oxidative stress-independent lysosomal impairment. (1st October 2021)

• Record Type: Journal Article
• Authors: Wang, Yan; Ma, Ying; Yao, Yongshuai; Liu, Qing; Pang, Yanting; Tang, Meng
• Is Part Of: Environmental pollution. Volume 286(2021)
• Publication Date: 2021-10-01
• Subjects: Particulate matter -- Autophagy -- Autophagic flux -- Lysosome -- Oxidative stress -- Cathepsin B (CTSB); Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.117295
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Ambient particulate matter (APM) has been authenticated to exert hazards on human vascular endothelial cells, including abnormal autophagy. However, the potential reasons for autophagosome accumulation are still obscure. Since autophagy is a dynamic process, it is imperative to systemically consider the autophagic induction combined with its degradation to reflect realistic scenarios. Therefore, in the current study, different exposure durations were initially employed for the detection of autophagic marker proteins to assess the dynamic autophagic state preliminarily. Additionally, LC3 turn-over and autophagic flux assays were used to determine the specific cause of LC3II upregulation in EA.hy926 human vascular endothelial cells by a type of standard urban particulate matter, PM SRM1648a. As a result, PM SRM1648a stimulates excess autophagic vacuoles in EA. hy926 cells, in which the underlying causes are probably different at varying incubation endpoints. Intriguingly, LC3II upregulation was due to the intensifying autophagic initiation after 6 h of exposure, whereas as exposure period was extended to 24 h, overloaded autophagic vacuoles were attributed to the defective autophagy. Mechanistically, PM SRM1648a damages EA. hy926 cells by inducing lysosomal disequilibrium and resultant autophagic malfunction which are not directly mediated by oxidative stress. These data indicate that appropriate maintenance of lysosomal function and autophagic flux is probably a protective measure against APM-induced endothelial cell damage. Graphical abstract: Image 1 Highlights: PM SRM1648a disrupts autophagic flux and triggers defective autophagy in EA. hy926 human endothelial cells. Accumulation of LC3II/autophagosomes can be attributed to different reasons at different exposure points. Autophagic ability and autophagic degradation are involved in LC3II upregulation at different time points. Lysosomal impairment plays a vital role in the dysfunction of autophagic flux in the case of PM SRM1648a. Oxidative stress is not the main reason for lysosomal hydrolyses inactivation caused by PM SRM1648a. Abstract : PM SRM1648a triggers defective autophagy in EA.hy926 vascular endothelial cells through oxidative stress-independent lysosomal impairment.