Rapid effects of diesel exhaust particulate extracts on intracellular signaling in human endothelial cells.
Inhalation of ultrafine particulate matter (PM) in air pollution increases cardiovascular mortality by passing into systemic circulation and possibly affecting endothelial cell (EC) function. This study identified the chemical constituents, including polycyclic aromatic hydrocarbons (PAHs), in diesel exhaust particulate extracts (DEPEs) prepared from a truck run at different speeds and engine loads. The short-term effects of DEPEs alone or in combination with estradiol (E(2)) on MAPK (ERK1/2), AKT, and eNOS activation and nitric oxide (NO) production in human umbilical vein EC (HUVEC) were evaluated. Notably, DEPE from a truck run under increasing loads (L) stimulated phosphorylation of MAPK, AKT, and eNOS whereas DEPE from the truck run at increasing speeds (S) did not affect MAPK alone, but inhibited E(2)-induced MAPK and eNOS phosphorylation. Higher PAH concentrations in the DEPE L versus DEPE S samples correlate with the observed differences in cellular activities. Like E(2), DEPEs rapidly increased NO with the DEPE L sample acting additively with E(2) and then inhibiting E(2)-induced NO with longer treatment time. Like E(2), DEPEs increased trans-endothelial electrical resistance (TEER) across a monolayer of HUVEC. These data are the first characterization of rapid effects of DEPE in human EC and may indicate mechanisms for diesel exhaust in vascular function.
Sumanasekera
Wasana K
WK
Department of Biochemistry & Molecular Biology and the Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Ivanova
Margarita M
MM
Johnston
Benjamin J
BJ
Dougherty
Susan M
SM
Sumanasekera
Gamini U
GU
Myers
Steven R
SR
Ali
Yeakub
Y
Kizu
Ryoichi
R
Klinge
Carolyn M
CM
D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000633:toxicity; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D001335:Vehicle Emissions; D009569:Nitric Oxide; D004958:Estradiol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases