title: Diesel Exhaust Particles Contribute to Endothelia Apoptosis via Autophagy Pathway.
abstract: Epidemiological studies suggest that an increase of PM2.5 diesel exhaust particles (DEP) in ambient air corresponds to increased myocardial infarctions and atherosclerosis. When exposed to DEP, endothelial cells exhibit increases in oxidative stress and apoptosis, but the role of autophagy in this DEP-induced cell death remains unclear. Here, we suggest that acute DEP exposure produces intracellular reactive oxygen species (ROS) leading to induction of DEP internalization, endothelial dysfunction, and pro-inflammation in an in vitro human umbilical vein endothelial cells (HUVEC) model. This study found that increases in intracellular oxidative stress and cellular internalization of DEP occurred within 2 h of exposure to DEP. After 2 h of DEP exposure, Mdm2 expression was increased, which triggered cellular autophagy after 4 h of DEP exposure and suppressed cellular senescence. Unfortunately, phagocytized DEP could not be eliminated by cellular autophagy, which led to a continuous buildup of ROS, an increased release of cytokines, and an increased expression of anchoring molecules. After 12 h of DEP exposure, HUVEC reduced Mdm2 expression leading to increased p53 expression, which triggered apoptosis and ultimately resulted in endothelial dysfunction. On the other hand, when cells lacked the ability to induce autophagy, DEP was unable to induce cell senescence and most of the cells survived with only a small percentage of the cells undergoing necrosis. The results presented in this study clearly demonstrate the role cellular autophagy plays in DEP-induced atherosclerosis.
authors.affiliation: Department of Bioscience Technology, College of Science.
authors.forename: Jhih-Syuan
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Center for Nanotechnology.|Department of Biomedical Engineering, College of Engineering, Chung Yuan Christian University, Zhongli District, Taoyuan City 32023, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Tseng
authors.affiliation: Department of Bioscience Technology, College of Science.|Center for Nanotechnology.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chao
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071192:Autophagy-Related Protein 12 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D053260:Soot / Q000737:chemistry / Q000633:toxicity; D014041:Tokyo; D014657:Vasculitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: C466624:ATG12 protein, human; D000393:Air Pollutants; D000071192:Autophagy-Related Protein 12; D015415:Biomarkers; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D053260:Soot; D001335:Vehicle Emissions; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: DEP; HUVEC; ROS; apoptosis.; autophagy