Sirtuin 3 Protects against Urban Particulate Matter-Induced Autophagy in Human Bronchial Epithelial Cells.

Abstract

Urban particulate matter (urban PM) is a heterogeneous mixture of various types of particles originating from different sources. Exposure to high concentrations of urban PM leading to adverse health effects is evaluated by using in vitro cultures of human lung epithelial cells. However, the mechanism underlying the correlation between high concentrations of urban PM exposure and adverse health effects has not been fully elucidated; urban PM-induced oxidative stress is considered as an important mechanism of urban PM-mediated cytotoxicity. Sirtuin 3 (SIRT3), a primary mitrochondrial deacetylase, controls cellular reactive oxygen species (ROS) production, and expression of antioxidant enzymes. In this study, we examined the role of SIRT3 in the regulation of urban PM-induced oxidative stress in normal primary human bronchial epithelial cells (HBEpiCs). Cell viability showed a time- and concentration-dependent decrease when exposed to urban PM, which could indicate that the amount of lactate dehydrogenase released from the cell in response to urban PM is related to cell viability in HBEpiC. The effects of urban PM on morphological and biochemical markers of autophagy in HBEpiC were analyzed by electron microscopy and Western blotting. Overexpression of SIRT3 inhibited urban PM-induced ROS generation, while concomitantly increasing the expression of antioxidant enzymes, and decreasing NF-κB activation and release of inflammation factors. Up-regulation of SIRT3 significantly inhibited the expression of autophagy markers and autophagic vacuole formation. Our findings provide a valuable insight into the potential role of the SIRT3 enzyme in regulating urban PM-induced autophagy by mediating urban PM-induced oxidative stress, which may contribute to urban PM-induced impairment of airway epithelial cell function.

• Authors: I-Chieh Chen, Hsin-Hsiu Huang, Pei-Fen Chen, Hung-Che Chiang
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 152 Issue 1 Pg. 113-27 (07 2016) ISSN: 1096-0929 [Electronic] United States
• PMID: 27125970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Antioxidants
• Particulate Matter
• Reactive Oxygen Species
• SIRT3 protein, human
• Sirtuin 3

Topics

• Antioxidants (metabolism)
• Autophagy (drug effects)
• Bronchi (drug effects, enzymology, pathology)
• Cell Survival (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, enzymology, pathology)
• Humans
• Inhalation Exposure
• Oxidative Stress (drug effects)
• Particulate Matter (toxicity)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Sirtuin 3 (genetics, metabolism)
• Time Factors
• Transfection
• Urban Health