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Arsenic induced an increase in endothelial cell permeability: involvement of cytoskeleton signaling.

Authors
Ward-R; Shi-X; Castranova-V; Qian-Y
Source
Toxicologist 2008 Mar; 102(1):334
NIOSHTIC No.
20033640
Abstract
Although it has been shown that human exposure to arsenic is related to an increase in inflammation, cardiovascular diseases, and cancers, the molecular mechanisms of its action remains to be elucidated. In this study, we demonstrated that exposure to arsenic caused an increase in cell permeability in human microvascular endothelial cells (HMEC), which is correlated with the remodeling of actin, microtubule cytoskeleton, and the activation of Erk1/2 signaling by the production of reactive oxygen species (ROS). Inhibition of Erk1/2 activities, blockage of actin filament remodeling, or removal of ROS partially suppressed the arsenic-induced permeability increase, indicating the involvement of cytoskeleton, Erk1/2, and ROS signaling pathways in arsenic-induced endothelial cell morphological changes. Furthermore, we found that arsenic treatment disrupted the localization of VE-cadherin at adherens junctions in HMEC and induced its translocation into the nucleus. Moreover, it was found that arsenic-induced VE-cadherin nuclear translocation was inhibited by treatments with ROS scavengers, and actin filament and microtubule inhibitors. Taken together, this study demonstrates that arsenic stimulation induces an increase in cell permeability in HMEC, which involves actin and microtubule cytoskeleton signaling. The results from this study may contribute to dissecting the molecular mechanisms involved in arsenic toxicity.
Keywords
Cardiovascular-system-disorders; Molecular-biology; Cell-wall-permeability; Toxic-effects; Toxins; Cell-morphology; Skeletal-system-disorders; Chemical-properties
CAS No.
7440-38-2
Publication Date
20080301
Document Type
Abstract
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
State
WV; WA
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