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Stress fibers, autophagy and necrosis by persistent exposure to PM2.5 from biomass combustion.
Dornhof, Regina; Maschowski, Christoph; Osipova, Anastasiya; Gieré, Reto; Seidl, Maximilian; Merfort, Irmgard; Humar, Matjaz.
Afiliação
  • Dornhof R; Institute of Pharmaceutical Sciences, Pharmaceutical Biology and Biotechnology, Albert-Ludwigs University Freiburg, Freiburg, Germany.
  • Maschowski C; Institute of Earth and Environmental Sciences, Albert-Ludwigs University Freiburg, Freiburg, Germany.
  • Osipova A; Institute of Pharmaceutical Sciences, Pharmaceutical Biology and Biotechnology, Albert-Ludwigs University Freiburg, Freiburg, Germany.
  • Gieré R; Department of Earth and Environmental Science and Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
  • Seidl M; Institute for Surgical Pathology, Faculty of Medicine, Albert-Ludwigs University Freiburg, Freiburg, Germany.
  • Merfort I; Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Albert-Ludwigs University Freiburg, Freiburg, Germany.
  • Humar M; Institute of Pharmaceutical Sciences, Pharmaceutical Biology and Biotechnology, Albert-Ludwigs University Freiburg, Freiburg, Germany.
PLoS One ; 12(7): e0180291, 2017.
Article em En | MEDLINE | ID: mdl-28671960
Fine particulate matter (PM2.5) can adversely affect human health. Emissions from residential energy sources have the largest impact on premature mortality globally, but their pathological and molecular implications on cellular physiology are still elusive. In the present study potential molecular consequences were investigated during long-term exposure of human bronchial epithelial BEAS-2B cells to PM2.5, collected from a biomass power plant. Initially, we observed that PM2.5 did not affect cellular survival or proliferation. However, it triggered an activation of the stress response p38 MAPK which, along with RhoA GTPase and HSP27, mediated morphological changes in BEAS-2B cells, including actin cytoskeletal rearrangements and paracellular gap formation. The p38 inhibitor SB203580 prevented phosphorylation of HSP27 and ameliorated morphological changes. During an intermediate phase of long-term exposure, PM2.5 triggered proliferative regression and activation of an adaptive stress response necessary to maintain energy homeostasis, including AMPK, repression of translational elongation, and autophagy. Finally, accumulation of intracellular PM2.5 promoted lysosomal destabilization and cell death, which was dependent on lysosomal hydrolases and p38 MAPK, but not on the inflammasome and pyroptosis. TEM images revealed formation of protrusions and cellular internalization of PM2.5, induction of autophagosomes, amphisomes, autophagosome-lysosomal fusion, multiple compartmental fusion, lysosomal burst, swollen mitochondria and finally necrosis. In consequence, persistent exposure to PM2.5 may impair epithelial barriers and reduce regenerative capacity. Hence, our results contribute to a better understanding of PM-associated lung and systemic diseases on the basis of molecular events.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Biomassa / Fibras de Estresse / Exposição Ambiental / Material Particulado Limite: Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Biomassa / Fibras de Estresse / Exposição Ambiental / Material Particulado Limite: Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Estados Unidos