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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Hypertension Unit, Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Michal S
authors.initials: MS
authors.lastname: Hoffmann
authors.forename: Prachi
authors.initials: P
authors.lastname: Singh
authors.forename: Robert
authors.initials: R
authors.lastname: Wolk
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Narkiewicz
authors.forename: Virend K
authors.initials: VK
authors.lastname: Somers
mesh_terms: D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D054638:Dual Specificity Phosphatase 1 / Q000097:blood*; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000097:blood*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D010100:Oxygen
keywords: Dual specificity phosphatase 1; Intermittent hypoxia; Obstructive sleep apnea; Reactive oxygen species