Combined Superoxide Dismutase/Catalase Mimetics Alter Fetal Pulmonary Arterial Smooth Muscle Cell Growth

Stephen Wedgwood, Stephen Matthew Black

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) are known to play an important role in the proliferation and viability of vascular smooth muscle cells. We have shown previously that treatment of fetal pulmonary arterial smooth muscle cells (FPASMC) with concentrations of 25 μM and higher of EUK-134, a superoxide dismutase/catalase mimetic, decreased cell viability via the induction of apoptosis. Here we demonstrate a dose-dependent decrease in serum-induced FPASMC growth at lower doses of EUK-134. This was due to the attenuation of FPASMC proliferation rather than the induction of apoptosis. Moreover, we found that the inhibition of FPASMC proliferation was observed using EUK-134 at concentrations as low as 5 μM. This inhibition of proliferation correlated with a 31% decrease in superoxide levels, as estimated using the oxidation of dihydroethidium. Flow cytometry revealed an increase in FPASMC in G2 after 24 h of exposure to 10 μM EUK-134. This was associated with a twofold increase in levels of the cell-cycle regulatory protein p21. This, together with our previous data, suggests that ROS levels determine the rate of FPASMC proliferation and, when below a threshold level, trigger apoptosis. Titration of ROS with antioxidants may help to prevent, or reverse, the vascular remodeling manifest in many cardiovascular disease states.

Original languageEnglish (US)
Pages (from-to)191-197
Number of pages7
JournalAntioxidants and Redox Signaling
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2004

Fingerprint

Cell growth
Catalase
Superoxide Dismutase
Smooth Muscle Myocytes
Muscle
Lung
Growth
Cell proliferation
Reactive Oxygen Species
Cells
Cell Proliferation
Apoptosis
Cell Cycle Proteins
Flow cytometry
Titration
Vascular Smooth Muscle
Superoxides
Cell Survival
Flow Cytometry
Cardiovascular Diseases

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Combined Superoxide Dismutase/Catalase Mimetics Alter Fetal Pulmonary Arterial Smooth Muscle Cell Growth. / Wedgwood, Stephen; Black, Stephen Matthew.

In: Antioxidants and Redox Signaling, Vol. 6, No. 1, 01.01.2004, p. 191-197.

Research output: Contribution to journalArticle

@article{85efd203505b4a788fd04d7652bb53e5,
title = "Combined Superoxide Dismutase/Catalase Mimetics Alter Fetal Pulmonary Arterial Smooth Muscle Cell Growth",
abstract = "Reactive oxygen species (ROS) are known to play an important role in the proliferation and viability of vascular smooth muscle cells. We have shown previously that treatment of fetal pulmonary arterial smooth muscle cells (FPASMC) with concentrations of 25 μM and higher of EUK-134, a superoxide dismutase/catalase mimetic, decreased cell viability via the induction of apoptosis. Here we demonstrate a dose-dependent decrease in serum-induced FPASMC growth at lower doses of EUK-134. This was due to the attenuation of FPASMC proliferation rather than the induction of apoptosis. Moreover, we found that the inhibition of FPASMC proliferation was observed using EUK-134 at concentrations as low as 5 μM. This inhibition of proliferation correlated with a 31{\%} decrease in superoxide levels, as estimated using the oxidation of dihydroethidium. Flow cytometry revealed an increase in FPASMC in G2 after 24 h of exposure to 10 μM EUK-134. This was associated with a twofold increase in levels of the cell-cycle regulatory protein p21. This, together with our previous data, suggests that ROS levels determine the rate of FPASMC proliferation and, when below a threshold level, trigger apoptosis. Titration of ROS with antioxidants may help to prevent, or reverse, the vascular remodeling manifest in many cardiovascular disease states.",
author = "Stephen Wedgwood and Black, {Stephen Matthew}",
year = "2004",
month = "1",
day = "1",
doi = "10.1089/152308604771978507",
language = "English (US)",
volume = "6",
pages = "191--197",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "1",

}

TY - JOUR

T1 - Combined Superoxide Dismutase/Catalase Mimetics Alter Fetal Pulmonary Arterial Smooth Muscle Cell Growth

AU - Wedgwood, Stephen

AU - Black, Stephen Matthew

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Reactive oxygen species (ROS) are known to play an important role in the proliferation and viability of vascular smooth muscle cells. We have shown previously that treatment of fetal pulmonary arterial smooth muscle cells (FPASMC) with concentrations of 25 μM and higher of EUK-134, a superoxide dismutase/catalase mimetic, decreased cell viability via the induction of apoptosis. Here we demonstrate a dose-dependent decrease in serum-induced FPASMC growth at lower doses of EUK-134. This was due to the attenuation of FPASMC proliferation rather than the induction of apoptosis. Moreover, we found that the inhibition of FPASMC proliferation was observed using EUK-134 at concentrations as low as 5 μM. This inhibition of proliferation correlated with a 31% decrease in superoxide levels, as estimated using the oxidation of dihydroethidium. Flow cytometry revealed an increase in FPASMC in G2 after 24 h of exposure to 10 μM EUK-134. This was associated with a twofold increase in levels of the cell-cycle regulatory protein p21. This, together with our previous data, suggests that ROS levels determine the rate of FPASMC proliferation and, when below a threshold level, trigger apoptosis. Titration of ROS with antioxidants may help to prevent, or reverse, the vascular remodeling manifest in many cardiovascular disease states.

AB - Reactive oxygen species (ROS) are known to play an important role in the proliferation and viability of vascular smooth muscle cells. We have shown previously that treatment of fetal pulmonary arterial smooth muscle cells (FPASMC) with concentrations of 25 μM and higher of EUK-134, a superoxide dismutase/catalase mimetic, decreased cell viability via the induction of apoptosis. Here we demonstrate a dose-dependent decrease in serum-induced FPASMC growth at lower doses of EUK-134. This was due to the attenuation of FPASMC proliferation rather than the induction of apoptosis. Moreover, we found that the inhibition of FPASMC proliferation was observed using EUK-134 at concentrations as low as 5 μM. This inhibition of proliferation correlated with a 31% decrease in superoxide levels, as estimated using the oxidation of dihydroethidium. Flow cytometry revealed an increase in FPASMC in G2 after 24 h of exposure to 10 μM EUK-134. This was associated with a twofold increase in levels of the cell-cycle regulatory protein p21. This, together with our previous data, suggests that ROS levels determine the rate of FPASMC proliferation and, when below a threshold level, trigger apoptosis. Titration of ROS with antioxidants may help to prevent, or reverse, the vascular remodeling manifest in many cardiovascular disease states.

UR - http://www.scopus.com/inward/record.url?scp=0346690282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346690282&partnerID=8YFLogxK

U2 - 10.1089/152308604771978507

DO - 10.1089/152308604771978507

M3 - Article

C2 - 14713351

AN - SCOPUS:0346690282

VL - 6

SP - 191

EP - 197

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 1

ER -