Atmospheric PM2.5 blocking up autophagic flux in HUVECs via inhibiting Sntaxin-17 and LAMP2.
Ecotoxicol Environ Saf
; 208: 111450, 2021 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-33039871
ABSTRACT
Despite of growing evidence linking PM2.5 exposure to autophagic activity in various human cells, the functional significance of PM2.5 exposure affecting autophagy in the pathogenesis of human cardiovascular disease and the underlying molecular mechanisms remain unclear. In this study, the effects of ambient PM2.5 (with final concentration 0, 1, 5, 25 µg/mL) on the autophagic activity in human umbilical vein endothelial cells (HUVECs) were systematically studied. The results showed that the internalized PM2.5 mainly localized in the membrane-surrounded vacuoles in the cytoplasm. Compared with the negative control, dose-dependent increase of autophagosomes, puncta and protein levels of LC3-II and p62, and both dose- and time-dependent increase of AKT phosphorylation, with inversely time-dependent reduction of Beclin 1, ATG3 and ATG5 proteins, were presented in the PM2.5-treated HUVECs, indicating a clear impairment of autophagic degradation in the PM2.5-exposed HUVECs. Meanwhile, increase in lysosomes, LAMP1, proteases of CTSB and CTSD, and protein phosphorylation of ERK1/2 and TFEB was identified in the PM2.5-treated HUVECs, showing a PM2.5-mediated enhancement in lysosomal activity. A novel finding in this study is that both Sntaxin-17 and LAMP2, two key proteins involved in the control of membrane fusion between autophagosome and lysosome, were significantly decreased in the PM2.5-exposed HUVECs, suggesting that the fusion of autophagosome-lysosome was blocked up. Collectively, ambient PM2.5 exposure may block up the autophagic flux in HUVECs through inhibiting the expression of Sntaxin-17 and LAMP2. Autophagic activity in HUVECs is a useful biomarker for assessing risks of environmental factors to human cardiovascular health.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poluentes Atmosféricos
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Proteína 2 de Membrana Associada ao Lisossomo
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Material Particulado
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article