Cytosolic NADH redox and thiol oxidation regulate pulmonary arterial force through ERK MAP kinase

Richard A. Oeckler, Elizabeth Arcuino, Mansoor Ahmad, Susan C. Olson, Michael S. Wolin

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

An ERK MAP kinase-mediated contractile mechanism previously reported to be activated by peroxide and stretch in bovine coronary arteries is shown in this study to be present in endothelium-denuded bovine pulmonary arteries and subject to regulation by modulation of cytosolic NAD(H) redox through the lactate dehydrogenase reaction. Although our previous work identified an acute Po 2-dependent peroxide-mediated relaxation of bovine pulmonary arteries on exposure to lactate, a 30-min treatment with 10 mM lactate enhanced ERK phosphorylation and increased force generation to 30 mM KCl. Hypoxia inhibited these responses to lactate. Increases in ERK phosphorylation and the enhancement of force generation by lactate and stretch are attenuated in the presence of inhibitors of Nox oxidase (0.1 mM apocynin) or ERK activation (10 μM PD-98059) and by 0.1 mM ebselen. Additionally, incubation of pulmonary arteries with 10 mM pyruvate lowered basal levels of ERK phosphorylation, and it inhibited both the ERK phosphorylation and the enhancement in force generation to 30 mM KCl caused by stretch. Treatment of pulmonary arteries with the thiol oxidant diamide (1 μM) elicited what appears to be a peroxide-independent increase in force and ERK phosphorylation that were both attenuated by PD-98059. Thus pulmonary arteries possess a peroxide-elicited contractile mechanism involving ERK MAP kinase, which is stimulated by stretch and regulated through the control of Nox oxidase activity by the availability of cytosolic NADH.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume288
Issue number6 32-6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Extracellular Signal-Regulated MAP Kinases
Sulfhydryl Compounds
NAD
Pulmonary Artery
Oxidation-Reduction
Peroxides
Phosphorylation
Lactic Acid
Lung
Oxidoreductases
Diamide
Pyruvic Acid
L-Lactate Dehydrogenase
Oxidants
Endothelium
Coronary Vessels
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Keywords

  • Diamide
  • Lactate
  • Nox
  • Peroxide
  • Stretch

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Cytosolic NADH redox and thiol oxidation regulate pulmonary arterial force through ERK MAP kinase. / Oeckler, Richard A.; Arcuino, Elizabeth; Ahmad, Mansoor; Olson, Susan C.; Wolin, Michael S.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 288, No. 6 32-6, 06.2005.

Research output: Contribution to journalArticle

Oeckler, Richard A. ; Arcuino, Elizabeth ; Ahmad, Mansoor ; Olson, Susan C. ; Wolin, Michael S. / Cytosolic NADH redox and thiol oxidation regulate pulmonary arterial force through ERK MAP kinase. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2005 ; Vol. 288, No. 6 32-6.
@article{3f6ae3f1a66c4e74b29326e1321825a1,
title = "Cytosolic NADH redox and thiol oxidation regulate pulmonary arterial force through ERK MAP kinase",
abstract = "An ERK MAP kinase-mediated contractile mechanism previously reported to be activated by peroxide and stretch in bovine coronary arteries is shown in this study to be present in endothelium-denuded bovine pulmonary arteries and subject to regulation by modulation of cytosolic NAD(H) redox through the lactate dehydrogenase reaction. Although our previous work identified an acute Po 2-dependent peroxide-mediated relaxation of bovine pulmonary arteries on exposure to lactate, a 30-min treatment with 10 mM lactate enhanced ERK phosphorylation and increased force generation to 30 mM KCl. Hypoxia inhibited these responses to lactate. Increases in ERK phosphorylation and the enhancement of force generation by lactate and stretch are attenuated in the presence of inhibitors of Nox oxidase (0.1 mM apocynin) or ERK activation (10 μM PD-98059) and by 0.1 mM ebselen. Additionally, incubation of pulmonary arteries with 10 mM pyruvate lowered basal levels of ERK phosphorylation, and it inhibited both the ERK phosphorylation and the enhancement in force generation to 30 mM KCl caused by stretch. Treatment of pulmonary arteries with the thiol oxidant diamide (1 μM) elicited what appears to be a peroxide-independent increase in force and ERK phosphorylation that were both attenuated by PD-98059. Thus pulmonary arteries possess a peroxide-elicited contractile mechanism involving ERK MAP kinase, which is stimulated by stretch and regulated through the control of Nox oxidase activity by the availability of cytosolic NADH.",
keywords = "Diamide, Lactate, Nox, Peroxide, Stretch",
author = "Oeckler, {Richard A.} and Elizabeth Arcuino and Mansoor Ahmad and Olson, {Susan C.} and Wolin, {Michael S.}",
year = "2005",
month = "6",
doi = "10.1152/ajplung.00223.2004",
language = "English (US)",
volume = "288",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "6 32-6",

}

TY - JOUR

T1 - Cytosolic NADH redox and thiol oxidation regulate pulmonary arterial force through ERK MAP kinase

AU - Oeckler, Richard A.

AU - Arcuino, Elizabeth

AU - Ahmad, Mansoor

AU - Olson, Susan C.

AU - Wolin, Michael S.

PY - 2005/6

Y1 - 2005/6

N2 - An ERK MAP kinase-mediated contractile mechanism previously reported to be activated by peroxide and stretch in bovine coronary arteries is shown in this study to be present in endothelium-denuded bovine pulmonary arteries and subject to regulation by modulation of cytosolic NAD(H) redox through the lactate dehydrogenase reaction. Although our previous work identified an acute Po 2-dependent peroxide-mediated relaxation of bovine pulmonary arteries on exposure to lactate, a 30-min treatment with 10 mM lactate enhanced ERK phosphorylation and increased force generation to 30 mM KCl. Hypoxia inhibited these responses to lactate. Increases in ERK phosphorylation and the enhancement of force generation by lactate and stretch are attenuated in the presence of inhibitors of Nox oxidase (0.1 mM apocynin) or ERK activation (10 μM PD-98059) and by 0.1 mM ebselen. Additionally, incubation of pulmonary arteries with 10 mM pyruvate lowered basal levels of ERK phosphorylation, and it inhibited both the ERK phosphorylation and the enhancement in force generation to 30 mM KCl caused by stretch. Treatment of pulmonary arteries with the thiol oxidant diamide (1 μM) elicited what appears to be a peroxide-independent increase in force and ERK phosphorylation that were both attenuated by PD-98059. Thus pulmonary arteries possess a peroxide-elicited contractile mechanism involving ERK MAP kinase, which is stimulated by stretch and regulated through the control of Nox oxidase activity by the availability of cytosolic NADH.

AB - An ERK MAP kinase-mediated contractile mechanism previously reported to be activated by peroxide and stretch in bovine coronary arteries is shown in this study to be present in endothelium-denuded bovine pulmonary arteries and subject to regulation by modulation of cytosolic NAD(H) redox through the lactate dehydrogenase reaction. Although our previous work identified an acute Po 2-dependent peroxide-mediated relaxation of bovine pulmonary arteries on exposure to lactate, a 30-min treatment with 10 mM lactate enhanced ERK phosphorylation and increased force generation to 30 mM KCl. Hypoxia inhibited these responses to lactate. Increases in ERK phosphorylation and the enhancement of force generation by lactate and stretch are attenuated in the presence of inhibitors of Nox oxidase (0.1 mM apocynin) or ERK activation (10 μM PD-98059) and by 0.1 mM ebselen. Additionally, incubation of pulmonary arteries with 10 mM pyruvate lowered basal levels of ERK phosphorylation, and it inhibited both the ERK phosphorylation and the enhancement in force generation to 30 mM KCl caused by stretch. Treatment of pulmonary arteries with the thiol oxidant diamide (1 μM) elicited what appears to be a peroxide-independent increase in force and ERK phosphorylation that were both attenuated by PD-98059. Thus pulmonary arteries possess a peroxide-elicited contractile mechanism involving ERK MAP kinase, which is stimulated by stretch and regulated through the control of Nox oxidase activity by the availability of cytosolic NADH.

KW - Diamide

KW - Lactate

KW - Nox

KW - Peroxide

KW - Stretch

UR - http://www.scopus.com/inward/record.url?scp=18844432265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18844432265&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00223.2004

DO - 10.1152/ajplung.00223.2004

M3 - Article

C2 - 15665044

AN - SCOPUS:18844432265

VL - 288

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 6 32-6

ER -