3 research outputs found
Use of X-ray Absorption Spectroscopy To Speciate Manganese in Airborne Particulate Matter from Five Counties Across the United States
The purpose of this study is to characterize manganese oxidation
states and speciation in airborne particulate matter (PM) and describe
how these potentially important determinants of PM toxicity vary by
location. Ambient PM samples were collected from five counties across
the US using a high volume sequential cyclone system that collects
PM in dry bulk form segregated into “coarse” and “fine”
size fractions. The fine fraction was analyzed for this study. Analyses
included total Mn using ICP-MS and characterization of oxidation states
and speciation using X-ray absorption spectroscopy (XAS). XAS spectra
of all samples and ten standard compounds of Mn were obtained at the
National Synchrotron Light Source. XAS data was analyzed using Linear
Combination Fitting (LCF). Results of the LCF analysis describe differences
in composition between samples. Mn(II) acetate and Mn(II) oxide are
present in all samples, while Mn(II) carbonate and Mn(IV) oxide are
absent. To the best of our knowledge, this is the first paper to characterize
Mn composition of ambient PM and examine differences between urban
sites in the US. Differences in oxidation state and composition indicate
regional variations in sources and atmospheric chemistry that may
help explain differences in health effects identified in epidemiological
studies
Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation
BACKGROUND:
Exposure to particulate matter (PM) is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation.
OBJECTIVES:
We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC) barrier integrity and enhanced cardiopulmonary dysfunction.
METHODS:
Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER) in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm). Biochemical assessment of ROS generation and Ca2+ mobilization were also measured.
RESULTS:
PM exposure induced tight junction protein Zona occludens-1 (ZO-1) relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin). N-acetyl-cysteine (NAC, 5 mM) reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2), in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro.
CONCLUSIONS:
These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes
Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation
Background: Exposure to particulate matter (PM) is a significant risk factor for increased cardiopulmonary morbidity
and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is
proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation.
Objectives: We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell
(EC) barrier integrity and enhanced cardiopulmonary dysfunction.
Methods: Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical
Resistance (TER) in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size
>0.1 μm). Biochemical assessment of ROS generation and Ca2+ mobilization were also measured.
Results: PM exposure induced tight junction protein Zona occludens-1 (ZO-1) relocation from the cell periphery,
which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins
(VE-cadherin and β-catenin). N-acetyl-cysteine (NAC, 5 mM) reduced PM-induced ROS generation in ECs, which
further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium
mobilization via the transient receptor potential cation channel M2 (TRPM2), in a ROS-dependent manner with
subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1
degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier
disruption and vascular hyperpermeability in vivo and in vitro.
Conclusions: These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated
calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel
mechanism for PM-induced lung damage and adverse cardiovascular outcomes