Comparative study of the effects of PM1-induced oxidative stress on autophagy and surfactant protein B and C expressions in lung alveolar type II epithelial MLE-12 cells

Biochim Biophys Acta. 2016 Dec;1860(12):2782-92. doi: 10.1016/j.bbagen.2016.05.020. Epub 2016 May 18.

Abstract

Background: There is a strong link between smaller air pollution particles and a range of serious health conditions. Thus, there is a need for understanding the impacts of airborne fine particulate matter (PM) with an aerodynamic diameter of <1μm (PM1) on lung alveolar epithelial cells. In the present study, mouse lung epithelial type II cell MLE-12 cells were used to examine the intracellular oxidative responses and the surfactant protein expressions after exposure to various concentrations of PM1 collected from an urban site and a steel-factory site (referred as uPM1 and sPM1 hereafter, respectively).

Methods: Physicochemical characterization of PM1 was performed by using scanning electron microscopy and transmission electron microscopy. Cytotoxicity and autophagy induced by PM1 were assessed by using comprehensive approaches after MLE-12 cells were exposed to different concentrations of PM1 for various times. Expression of surfactant proteins B and C in MLE-12 cells was determined by Western blotting.

Results: All of the tested PM1 induced cytotoxicity evidenced by significant decrease of cell viability and increase of lactate dehydrogenase (LDH) release in a time- and concentration-dependent manner in the exposed cells compared with the unexposed cells. A similar pattern of increase of intercellular reactive oxygen species (ROS) generation and decrease of superoxide dismutase (SOD) and catalase (CAT) activities was also observed. PM1-induced autophagy was evidenced by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3II, and increased levels of beclin1. Data from Western blotting showed significant decrease of surfactant protein B and C expressions. Relatively high concentrations of transition metals, including Fe, Cu and Mn, may be responsible for the higher toxicity of sPM1 compared with uPM1. Moreover, pretreatment with N-acetylcysteine (NAC) or Chelex (a metal chelating agent, which removes a large suite of metals from PM1) prevented the increase of PM1-inudced ROS generation and autophagy, and down-regulated the expression of surfactant proteins B and C.

Conclusion: PM1, particularly PM1 with high concentrations of transition metals, such as Fe, Cu and Mn, induces oxidative damage and autophagy, as well as inhibits surfactant protein B and C expressions in lung alveolar type II epithelial cells.

General significance: This study will help to understand the mechanism underlying the toxicological effects of PM1 in lung alveolar type II epithelial cells. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.

Keywords: Alveolar epithelial cells; Autophagy; PM(1); ROS; Surfactant protein B/C.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Alveolar Epithelial Cells / cytology
  • Alveolar Epithelial Cells / drug effects*
  • Alveolar Epithelial Cells / metabolism
  • Animals
  • Autophagy / drug effects
  • Autophagy / genetics
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Gene Expression Regulation
  • Hydrogen Peroxide / pharmacology
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism
  • Metallurgy
  • Metals, Heavy / analysis
  • Metals, Heavy / toxicity*
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Oxidative Stress / drug effects
  • Particle Size
  • Particulate Matter / antagonists & inhibitors
  • Particulate Matter / isolation & purification
  • Particulate Matter / toxicity*
  • Pulmonary Surfactant-Associated Protein B / antagonists & inhibitors
  • Pulmonary Surfactant-Associated Protein B / biosynthesis*
  • Pulmonary Surfactant-Associated Protein B / genetics
  • Pulmonary Surfactant-Associated Protein C / antagonists & inhibitors
  • Pulmonary Surfactant-Associated Protein C / biosynthesis*
  • Pulmonary Surfactant-Associated Protein C / genetics
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Beclin-1
  • Becn1 protein, mouse
  • Map1lc3b protein, mouse
  • Metals, Heavy
  • Microtubule-Associated Proteins
  • Particulate Matter
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • Hydrogen Peroxide
  • L-Lactate Dehydrogenase
  • Catalase
  • Superoxide Dismutase
  • Acetylcysteine