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Hydrogen peroxide formation and actin filament reorganization by Cdc42 are essential for ethanol-induced in vitro angiogenesis.

Authors
Qian-Y; Luo-J; Leonard-SS; Harris-GK; Millecchia-L; Flynn-DC; Shi-X
Source
J Biol Chem 2003 May; 2(18):16189-16197
NIOSHTIC No.
20023294
Abstract
This report focuses on the identification of the molecular mechanisms of ethanol-induced in vitro angiogenesis. The manipulation of angiogenesis is an important therapeutic approach for the treatment of cancer, cardiovascular diseases, and chronic inflammation. Our results showed that ethanol stimulation altered the integrity of actin filaments and increased the formation of lamellipodia and filopodia in SVEC4-10 cells. Further experiments demonstrated that ethanol stimulation increased cell migration and invasion and induced in vitro angiogenesis in SVEC4-10 cells. Mechanistically, ethanol stimulation activated Cdc42 and produced H(2)O(2) a reactive oxygen species intermediate in SVEC4-10 cells. Measuring the time course of Cdc42 activation and H(2)O(2) production upon ethanol stimulation revealed that the Cdc42 activation and the increase of H(2)O(2) lasted more than 3 h, which indicates the mechanisms of the long duration effects of ethanol on the cells. Furthermore, either overexpression of a constitutive dominant negative Cdc42 or inhibition of H(2)O(2) production abrogated the effects of ethanol on SVEC4-10 cells, indicating that both the activation of Cdc42 and the production of H(2)O(2) are essential for the actions of ethanol. Interestingly, we also found that overexpression of a constitutive dominant positive Cdc42 itself was sufficient to produce H(2)O(2) and to induce in vitro angiogenesis. Taken together, our results suggest that ethanol stimulation can induce H(2)O(2) production through the activation of Cdc42, which results in reorganizing actin filaments and increasing cell motility and in vitro angiogenesis.
Keywords
In-vitro-studies; Alcohol-poisoning; Cancer; Cardiovascular-disease; Ethanols; Heart; Cell-migration; Proteins; Animal-studies
Contact
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
CODEN
JBCHA3
CAS No.
64-17-5
Publication Date
20030502
Document Type
Journal Article
Email Address
yaq2@cdc.gov
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
18
ISSN
0021-9258
NIOSH Division
HELD
Source Name
Journal of Biological Chemistry
State
WV
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