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

Yong Qian; Jia Luo; Stephen S Leonard; Gabriel K Harris; Lyndell Millecchia; Daniel C Flynn; Xianglin Shi

doi:10.1074/jbc.M207517200

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

Journal article

Open access

Peer reviewed

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

Yong Qian, Jia Luo, Stephen S Leonard, Gabriel K Harris, Lyndell Millecchia, Daniel C Flynn and Xianglin Shi

The Journal of biological chemistry, Vol.278(18), pp.16189-16197

05/02/2003

DOI: 10.1074/jbc.M207517200

PMID: 12598535

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https://doi.org/10.1074/jbc.M207517200View

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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.

Actins - chemistry

Actins - drug effects

Animals

cdc42 GTP-Binding Protein - physiology

Cell Line

Cell Movement - drug effects

Ethanol - toxicity

Hydrogen Peroxide - metabolism

Mice

Neovascularization, Physiologic - drug effects

Details

Title: Subtitle: Hydrogen peroxide formation and actin filament reorganization by Cdc42 are essential for ethanol-induced in vitro angiogenesis
Creators: Yong Qian - National Institute for Occupational Safety and Health
Jia Luo - West Virginia University
Stephen S Leonard - National Institute for Occupational Safety and Health
Gabriel K Harris - National Institute for Occupational Safety and Health
Lyndell Millecchia - National Institute for Occupational Safety and Health
Daniel C Flynn - National Institute for Occupational Safety and Health
Xianglin Shi - National Institute for Occupational Safety and Health
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.278(18), pp.16189-16197
DOI: 10.1074/jbc.M207517200
PMID: 12598535
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 05/02/2003
Academic Unit: Pathology
Record Identifier: 9984186482002771

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