Obstructive sleep apnea and intermittent hypoxia increase expression of dual specificity phosphatase 1

Michal S. Hoffmann, Prachi Singh, Robert Wolk, Krzysztof Narkiewicz, Virend Somers

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: Dual specificity phosphatase 1 (DUSP1) inhibits mitogen activated protein kinase activity, and is activated by several stimuli such as sustained hypoxia, oxidative stress, and hormones. However, the effect of intermittent hypoxia is not known. The aim of this study was to evaluate the role of intermittent hypoxia on DUSP1 expression, and to validate its role in a human model of intermittent hypoxia, as seen in obstructive sleep apnea (OSA). OSA is characterized by recurrent episodes of hypoxemia/reoxygenation and is a known risk factor for cardiovascular morbidity. Methods: In-vitro studies using human coronary artery endothelial cells (HCAEC) and ex-vivo studies using white blood cells isolated from healthy and OSA subjects. Results: Intermittent hypoxia induced DUSP1 expression in human coronary artery endothelial cells (HCAEC), and in granulocytes isolated from healthy human subjects. Functionally, DUSP1 increased the expression and activity of manganese superoxide dismutase (MnSOD) in HCAEC. Further, significant increases in DUSP1 mRNA from total blood, and in DUSP1 protein in mononuclear cells and granulocytes isolated from OSA subjects, were observed in the early morning hours after one night of intermittent hypoxemia due to untreated OSA. This early-morning OSA-induced augmentation of DUSP1 gene expression was attenuated by continuous positive airway pressure (CPAP) treatment of OSA. Conclusion: Intermittent hypoxia increases MnSOD activity via increased DUSP1 expression in HCAEC. Similarly, overnight intermittent hypoxemia in patients with OSA induces expression of DUSP1, which may mediate increases of MnSOD expression and activity. This may contribute significantly to neutralizing the effects of reactive oxygen species, a consequence of the intermittent hypoxemia/reperfusion elicited by OSA.

Original languageEnglish (US)
Pages (from-to)378-383
Number of pages6
JournalAtherosclerosis
Volume231
Issue number2
DOIs
StatePublished - Dec 2013

Fingerprint

Dual Specificity Phosphatase 1
Obstructive Sleep Apnea
Coronary Vessels
Endothelial Cells
Superoxide Dismutase
Granulocytes
Hypoxia
Continuous Positive Airway Pressure
Mitogen-Activated Protein Kinases
Reperfusion
Reactive Oxygen Species
Healthy Volunteers
Oxidative Stress
Leukocytes

Keywords

  • Dual specificity phosphatase 1
  • Intermittent hypoxia
  • Obstructive sleep apnea
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Obstructive sleep apnea and intermittent hypoxia increase expression of dual specificity phosphatase 1. / Hoffmann, Michal S.; Singh, Prachi; Wolk, Robert; Narkiewicz, Krzysztof; Somers, Virend.

In: Atherosclerosis, Vol. 231, No. 2, 12.2013, p. 378-383.

Research output: Contribution to journalArticle

Hoffmann, Michal S. ; Singh, Prachi ; Wolk, Robert ; Narkiewicz, Krzysztof ; Somers, Virend. / Obstructive sleep apnea and intermittent hypoxia increase expression of dual specificity phosphatase 1. In: Atherosclerosis. 2013 ; Vol. 231, No. 2. pp. 378-383.
@article{3555b5b590374ed595ccb90a13b72cd8,
title = "Obstructive sleep apnea and intermittent hypoxia increase expression of dual specificity phosphatase 1",
abstract = "Objective: Dual specificity phosphatase 1 (DUSP1) inhibits mitogen activated protein kinase activity, and is activated by several stimuli such as sustained hypoxia, oxidative stress, and hormones. However, the effect of intermittent hypoxia is not known. The aim of this study was to evaluate the role of intermittent hypoxia on DUSP1 expression, and to validate its role in a human model of intermittent hypoxia, as seen in obstructive sleep apnea (OSA). OSA is characterized by recurrent episodes of hypoxemia/reoxygenation and is a known risk factor for cardiovascular morbidity. Methods: In-vitro studies using human coronary artery endothelial cells (HCAEC) and ex-vivo studies using white blood cells isolated from healthy and OSA subjects. Results: Intermittent hypoxia induced DUSP1 expression in human coronary artery endothelial cells (HCAEC), and in granulocytes isolated from healthy human subjects. Functionally, DUSP1 increased the expression and activity of manganese superoxide dismutase (MnSOD) in HCAEC. Further, significant increases in DUSP1 mRNA from total blood, and in DUSP1 protein in mononuclear cells and granulocytes isolated from OSA subjects, were observed in the early morning hours after one night of intermittent hypoxemia due to untreated OSA. This early-morning OSA-induced augmentation of DUSP1 gene expression was attenuated by continuous positive airway pressure (CPAP) treatment of OSA. Conclusion: Intermittent hypoxia increases MnSOD activity via increased DUSP1 expression in HCAEC. Similarly, overnight intermittent hypoxemia in patients with OSA induces expression of DUSP1, which may mediate increases of MnSOD expression and activity. This may contribute significantly to neutralizing the effects of reactive oxygen species, a consequence of the intermittent hypoxemia/reperfusion elicited by OSA.",
keywords = "Dual specificity phosphatase 1, Intermittent hypoxia, Obstructive sleep apnea, Reactive oxygen species",
author = "Hoffmann, {Michal S.} and Prachi Singh and Robert Wolk and Krzysztof Narkiewicz and Virend Somers",
year = "2013",
month = "12",
doi = "10.1016/j.atherosclerosis.2013.09.033",
language = "English (US)",
volume = "231",
pages = "378--383",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Obstructive sleep apnea and intermittent hypoxia increase expression of dual specificity phosphatase 1

AU - Hoffmann, Michal S.

AU - Singh, Prachi

AU - Wolk, Robert

AU - Narkiewicz, Krzysztof

AU - Somers, Virend

PY - 2013/12

Y1 - 2013/12

N2 - Objective: Dual specificity phosphatase 1 (DUSP1) inhibits mitogen activated protein kinase activity, and is activated by several stimuli such as sustained hypoxia, oxidative stress, and hormones. However, the effect of intermittent hypoxia is not known. The aim of this study was to evaluate the role of intermittent hypoxia on DUSP1 expression, and to validate its role in a human model of intermittent hypoxia, as seen in obstructive sleep apnea (OSA). OSA is characterized by recurrent episodes of hypoxemia/reoxygenation and is a known risk factor for cardiovascular morbidity. Methods: In-vitro studies using human coronary artery endothelial cells (HCAEC) and ex-vivo studies using white blood cells isolated from healthy and OSA subjects. Results: Intermittent hypoxia induced DUSP1 expression in human coronary artery endothelial cells (HCAEC), and in granulocytes isolated from healthy human subjects. Functionally, DUSP1 increased the expression and activity of manganese superoxide dismutase (MnSOD) in HCAEC. Further, significant increases in DUSP1 mRNA from total blood, and in DUSP1 protein in mononuclear cells and granulocytes isolated from OSA subjects, were observed in the early morning hours after one night of intermittent hypoxemia due to untreated OSA. This early-morning OSA-induced augmentation of DUSP1 gene expression was attenuated by continuous positive airway pressure (CPAP) treatment of OSA. Conclusion: Intermittent hypoxia increases MnSOD activity via increased DUSP1 expression in HCAEC. Similarly, overnight intermittent hypoxemia in patients with OSA induces expression of DUSP1, which may mediate increases of MnSOD expression and activity. This may contribute significantly to neutralizing the effects of reactive oxygen species, a consequence of the intermittent hypoxemia/reperfusion elicited by OSA.

AB - Objective: Dual specificity phosphatase 1 (DUSP1) inhibits mitogen activated protein kinase activity, and is activated by several stimuli such as sustained hypoxia, oxidative stress, and hormones. However, the effect of intermittent hypoxia is not known. The aim of this study was to evaluate the role of intermittent hypoxia on DUSP1 expression, and to validate its role in a human model of intermittent hypoxia, as seen in obstructive sleep apnea (OSA). OSA is characterized by recurrent episodes of hypoxemia/reoxygenation and is a known risk factor for cardiovascular morbidity. Methods: In-vitro studies using human coronary artery endothelial cells (HCAEC) and ex-vivo studies using white blood cells isolated from healthy and OSA subjects. Results: Intermittent hypoxia induced DUSP1 expression in human coronary artery endothelial cells (HCAEC), and in granulocytes isolated from healthy human subjects. Functionally, DUSP1 increased the expression and activity of manganese superoxide dismutase (MnSOD) in HCAEC. Further, significant increases in DUSP1 mRNA from total blood, and in DUSP1 protein in mononuclear cells and granulocytes isolated from OSA subjects, were observed in the early morning hours after one night of intermittent hypoxemia due to untreated OSA. This early-morning OSA-induced augmentation of DUSP1 gene expression was attenuated by continuous positive airway pressure (CPAP) treatment of OSA. Conclusion: Intermittent hypoxia increases MnSOD activity via increased DUSP1 expression in HCAEC. Similarly, overnight intermittent hypoxemia in patients with OSA induces expression of DUSP1, which may mediate increases of MnSOD expression and activity. This may contribute significantly to neutralizing the effects of reactive oxygen species, a consequence of the intermittent hypoxemia/reperfusion elicited by OSA.

KW - Dual specificity phosphatase 1

KW - Intermittent hypoxia

KW - Obstructive sleep apnea

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=84888094948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888094948&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2013.09.033

DO - 10.1016/j.atherosclerosis.2013.09.033

M3 - Article

C2 - 24267255

AN - SCOPUS:84888094948

VL - 231

SP - 378

EP - 383

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 2

ER -