Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10).
This review focuses on the potential role that oxidative stress plays in the adverse effects of PM(10). The central hypothesis is that the ability of PM(10) to cause oxidative stress underlies the association between increased exposure to PM(10) and both exacerbations of lung disease and lung cancer. Pulmonary inflammation may also underlie the cardiovascular effects seen following increased PM(10), although the mechanisms of the cardiovascular effects of PM(10) are not well understood. PM(10) is a complex mix of various particle types and several of the components of PM(10) are likely to be involved in the induction of oxidative stress. The most likely of these are transition metals, ultrafine particle surfaces, and organic compounds. In support of this hypothesis, oxidative stress arising from PM(10) has been shown to activate a number of redox-responsive signaling pathways in lung target cells. These pathways are involved in expression of genes that play a role in responses relevant to inflammation and pathological change, including MAPKs, NF-kappaB, AP-1, and histone acetylation. Oxidative stress from particles is also likely to play an important role in the carcinogenic effects associated with PM(10) and hydroxyl radicals from PM(10) cause DNA damage in vitro.
Donaldson
Ken
K
Colt/ELEGI Laboratories, Centre for Inflammation Research, The University of Edinburgh Medical School, Edinburgh EH8 9AG, Scotland, UK. ken.donaldson@ed.ac.uk
Stone
Vicki
V
Borm
Paul J A
PJ
Jimenez
Luis A
LA
Gilmour
Peter S
PS
Schins
Roel P F
RP
Knaapen
Ad M
AM
Rahman
Irfan
I
Faux
Stephen P
SP
Brown
David M
DM
MacNee
William
W
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D004785:Environmental Pollutants / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D002118:Calcium