Urban particulate matter causes ER stress and the unfolded protein response in human lung cells.
Toxicol Sci
; 112(1): 111-22, 2009 Nov.
Article
en En
| MEDLINE
| ID: mdl-19675143
ABSTRACT
Because of its presumed adverse health effects, particulate air pollution (PM) has received growing attention, but the cellular mechanisms by which PM exerts toxicity are not well elucidated. PM has been associated with early mortality from illnesses that share endoplasmic reticulum (ER) stress as a mechanism of pathogenesis. In this study, we examined whether PM would induce the unfolded protein response (UPR) which is a cellular response to ER stress. Coarse (PM(10)) and fine (PM(2.5)) PM was collected from a single location in Northern Utah's Cache Valley during atmospheric inversions occurring in January 2002 and January 2003. Extracts of PM samples were added (12.5 and 25 microg/ml) to cultured human bronchial epithelial (BEAS-2B) cells for 24 h. At these concentrations neither PM nor LPS exhibited demonstrable cytotoxicity by the neutral red assay. However, PM elicited significant increases of unfolded protein response (UPR)-related post-translational modifications, such as S6 ribosomal protein, heat-shock protein (Hsp)27, and protein kinase related protein phosphorylation and cleavage of activating transcription factor (ATF)-6. PM exposure also resulted in significant increases in the UPR-associated proteins ATF-4, Hsp70, Hsp90, and binding immunoglobulin protein. PM also interfered with the export of Hsp70 from the cells in a concentration-dependent manner and resulted in release of C-reactive protein. Calpain was upregulated and activated in PM-treated cultures, though these events were not proapoptotic. This study demonstrates that PM is capable of inducing ER stress and the UPR in vitro and may be a mechanism by which PM exerts toxicity.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Salud Urbana
/
Contaminantes Atmosféricos
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Retículo Endoplásmico
/
Pulmón
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
Toxicol Sci
Asunto de la revista:
TOXICOLOGIA
Año:
2009
Tipo del documento:
Article