Arsenic alters vascular smooth muscle cell focal adhesion complexes leading to activation of FAK-src mediated pathways

Michele D. Pysher, Qin Chen, Richard Vaillancourt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Chronic exposure to arsenic has been linked to tumorigenesis, cardiovascular disease, hypertension, atherosclerosis, and peripheral vascular disease; however, the molecular mechanisms underlying its pathological effects remain elusive. In this study, we investigated arsenic-induced alteration of focal adhesion protein complexes in normal, primary vascular smooth muscle cells. We demonstrate that exposure to environmentally relevant concentrations of arsenic (50 ppb As3+) can alter focal adhesion protein co-association leading to activation of downstream pathways. Co-associated proteins were identified and quantitated via co-immunoprecipitation, SDS-PAGE, and Western blot analysis followed by scanning densitometry. Activation of MAPK pathways in total cell lysates was evaluated using phosphor-specific antibodies. In our model, arsenic treatment caused a sustained increase in FAK-src association and activation, and induced the formation of unique signaling complexes (beginning after 3-hour As3+ exposure and continuing throughout the 12-hour time course studied). The effects of these alterations were manifested as chronic stimulation of downstream PAK, ERK and JNK pathways. Past studies have demonstrated that these pathways are involved in cellular survival, growth, proliferation, and migration in VSMCs.

Original languageEnglish (US)
Pages (from-to)135-141
Number of pages7
JournalToxicology and Applied Pharmacology
Volume231
Issue number2
DOIs
StatePublished - Sep 1 2008

Fingerprint

Focal Adhesions
Arsenic
Vascular Smooth Muscle
Cell Adhesion
Smooth Muscle Myocytes
Muscle
Adhesion
Chemical activation
Cells
MAP Kinase Signaling System
Association reactions
Proteins
Peripheral Vascular Diseases
Densitometry
Immunoprecipitation
Phosphors
Polyacrylamide Gel Electrophoresis
Atherosclerosis
Carcinogenesis
Cardiovascular Diseases

Keywords

  • Arsenic
  • FAK
  • Focal adhesion
  • Src
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

@article{27780147bd3842838d00438239069fca,
title = "Arsenic alters vascular smooth muscle cell focal adhesion complexes leading to activation of FAK-src mediated pathways",
abstract = "Chronic exposure to arsenic has been linked to tumorigenesis, cardiovascular disease, hypertension, atherosclerosis, and peripheral vascular disease; however, the molecular mechanisms underlying its pathological effects remain elusive. In this study, we investigated arsenic-induced alteration of focal adhesion protein complexes in normal, primary vascular smooth muscle cells. We demonstrate that exposure to environmentally relevant concentrations of arsenic (50 ppb As3+) can alter focal adhesion protein co-association leading to activation of downstream pathways. Co-associated proteins were identified and quantitated via co-immunoprecipitation, SDS-PAGE, and Western blot analysis followed by scanning densitometry. Activation of MAPK pathways in total cell lysates was evaluated using phosphor-specific antibodies. In our model, arsenic treatment caused a sustained increase in FAK-src association and activation, and induced the formation of unique signaling complexes (beginning after 3-hour As3+ exposure and continuing throughout the 12-hour time course studied). The effects of these alterations were manifested as chronic stimulation of downstream PAK, ERK and JNK pathways. Past studies have demonstrated that these pathways are involved in cellular survival, growth, proliferation, and migration in VSMCs.",
keywords = "Arsenic, FAK, Focal adhesion, Src, Vascular smooth muscle cell",
author = "Pysher, {Michele D.} and Qin Chen and Richard Vaillancourt",
year = "2008",
month = "9",
day = "1",
doi = "10.1016/j.taap.2008.04.002",
language = "English (US)",
volume = "231",
pages = "135--141",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Arsenic alters vascular smooth muscle cell focal adhesion complexes leading to activation of FAK-src mediated pathways

AU - Pysher, Michele D.

AU - Chen, Qin

AU - Vaillancourt, Richard

PY - 2008/9/1

Y1 - 2008/9/1

N2 - Chronic exposure to arsenic has been linked to tumorigenesis, cardiovascular disease, hypertension, atherosclerosis, and peripheral vascular disease; however, the molecular mechanisms underlying its pathological effects remain elusive. In this study, we investigated arsenic-induced alteration of focal adhesion protein complexes in normal, primary vascular smooth muscle cells. We demonstrate that exposure to environmentally relevant concentrations of arsenic (50 ppb As3+) can alter focal adhesion protein co-association leading to activation of downstream pathways. Co-associated proteins were identified and quantitated via co-immunoprecipitation, SDS-PAGE, and Western blot analysis followed by scanning densitometry. Activation of MAPK pathways in total cell lysates was evaluated using phosphor-specific antibodies. In our model, arsenic treatment caused a sustained increase in FAK-src association and activation, and induced the formation of unique signaling complexes (beginning after 3-hour As3+ exposure and continuing throughout the 12-hour time course studied). The effects of these alterations were manifested as chronic stimulation of downstream PAK, ERK and JNK pathways. Past studies have demonstrated that these pathways are involved in cellular survival, growth, proliferation, and migration in VSMCs.

AB - Chronic exposure to arsenic has been linked to tumorigenesis, cardiovascular disease, hypertension, atherosclerosis, and peripheral vascular disease; however, the molecular mechanisms underlying its pathological effects remain elusive. In this study, we investigated arsenic-induced alteration of focal adhesion protein complexes in normal, primary vascular smooth muscle cells. We demonstrate that exposure to environmentally relevant concentrations of arsenic (50 ppb As3+) can alter focal adhesion protein co-association leading to activation of downstream pathways. Co-associated proteins were identified and quantitated via co-immunoprecipitation, SDS-PAGE, and Western blot analysis followed by scanning densitometry. Activation of MAPK pathways in total cell lysates was evaluated using phosphor-specific antibodies. In our model, arsenic treatment caused a sustained increase in FAK-src association and activation, and induced the formation of unique signaling complexes (beginning after 3-hour As3+ exposure and continuing throughout the 12-hour time course studied). The effects of these alterations were manifested as chronic stimulation of downstream PAK, ERK and JNK pathways. Past studies have demonstrated that these pathways are involved in cellular survival, growth, proliferation, and migration in VSMCs.

KW - Arsenic

KW - FAK

KW - Focal adhesion

KW - Src

KW - Vascular smooth muscle cell

UR - http://www.scopus.com/inward/record.url?scp=49549110251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49549110251&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2008.04.002

DO - 10.1016/j.taap.2008.04.002

M3 - Article

C2 - 18486177

AN - SCOPUS:49549110251

VL - 231

SP - 135

EP - 141

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 2

ER -