title: Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation.
abstract: Exposure to particulate air pollution is linked to increased incidences of cardiovascular diseases. Ambient ultrafine particles (UFP) from diesel vehicle engines have been shown to be proatherogenic in ApoE knockout mice and may constitute a major cardiovascular risk in humans. We posited that circulating nano-sized particles from traffic pollution sources induce vascular oxidative stress via JNK activation in endothelial cells. Diesel UFP were collected from a 1998 Kenworth truck. Intracellular superoxide assay revealed that these UFP dose-dependently induced superoxide (O(2)(-)) production in human aortic endothelial cells (HAEC). Flow cytometry showed that UFP increased MitoSOX red intensity specific for mitochondrial superoxide. Protein carbonyl content was increased by UFP as an indication of vascular oxidative stress. UFP also up-regulated heme oxygenase-1 (HO-1) and tissue factor (TF) mRNA expression, and pretreatment with the antioxidant N-acetylcysteine significantly decreased their expression. Furthermore, UFP transiently activated JNK in HAEC. Treatment with the JNK inhibitor SP600125 and silencing of both JNK1 and JNK2 with siRNA inhibited UFP-stimulated O(2)(-) production and mRNA expression of HO-1 and TF. Our findings suggest that JNK activation plays an important role in UFP-induced oxidative stress and stress response gene expression.
authors.affiliation: Department of Biomedical Engineering and Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Rongsong
authors.initials: R
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ning
authors.forename: Jeffery
authors.initials: J
authors.lastname: Cui
authors.forename: Bhavraj
authors.initials: B
authors.lastname: Khalsa
authors.forename: Lisong
authors.initials: L
authors.lastname: Ai
authors.forename: Wakako
authors.initials: W
authors.lastname: Takabe
authors.forename: Tyler
authors.initials: T
authors.lastname: Beebe
authors.forename: Rohit
authors.initials: R
authors.lastname: Majumdar
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Tzung
authors.initials: T
authors.lastname: Hsiai
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D001011:Aorta / Q000473:pathology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005742:Gasoline; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053758:Nanoparticles; D018384:Oxidative Stress; D052638:Particulate Matter / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism
chemical_list: D000873:Anthracenes; D005742:Gasoline; D052638:Particulate Matter; D034741:RNA, Small Interfering; D013481:Superoxides; C432165:pyrazolanthrone; D013925:Thromboplastin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D000111:Acetylcysteine