Shear stress regulation of endothelial NOS in fetal pulmonary arterial endothelial cells involves PKC

Stephen Wedgwood, Janine M. Bekker, Stephen M. Black

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

We have shown that increased pulmonary blood flow at birth increases the activity and expression of endothelial nitric oxide (NO) synthase (eNOS). However, the signal transduction pathway regulating this process is unclear. Because protein kinase C (PKC) has been shown to be activated in response to shear stress, we undertook a study to examine its role in mediating shear stress effects on eNOS. Initial experiments demonstrated that PKC activity increased in response to shear stress. NO production in response to shear stress was found to be biphasic, with an increase in NO release up to 1 h, a plateau phase until 4 h, and another increase between 4 and 8 h. PKC inhibition reduced the initial rise in NO release by 50% and the second increase by 70%. eNOS mRNA and protein levels were also increased in response to shear stress, whereas PKC inhibition prevented this increase. The stimulation of PKC activity with phorbol ester increased eNOS gene expression without increasing NO release. These results suggest that PKC may play different roles in shear stress-mediated release of NO and increased eNOS gene expression.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number2 25-2
StatePublished - Aug 29 2001

Fingerprint

Protein Kinase C
Endothelial Cells
Nitric Oxide
Lung
Gene Expression
Nitric Oxide Synthase Type III
Phorbol Esters
Heat-Shock Proteins
Signal Transduction
Parturition
Messenger RNA
Proteins

Keywords

  • Gene regulation
  • Nitric oxide synthase
  • Protein kinase C
  • Pulmonary blood flow
  • Signal transduction

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Shear stress regulation of endothelial NOS in fetal pulmonary arterial endothelial cells involves PKC. / Wedgwood, Stephen; Bekker, Janine M.; Black, Stephen M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 281, No. 2 25-2, 29.08.2001.

Research output: Contribution to journalArticle

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