S. Wedgwood et al., Shear stress regulation of endothelial NOS in fetal pulmonary arterial endothelial cells involves PKC, AM J P-LUNG, 281(2), 2001, pp. L490-L498
Citations number
55
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
We have shown that increased pulmonary blood flow at birth increases the ac
tivity and expression of endothelial nitric oxide (NO) synthase (eNOS). How
ever, the signal transduction pathway regulating this process is unclear. B
ecause 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 s
tress 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 inhib
ition 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 sh
ear 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 ro
les in shear stress-mediated release of NO and increased eNOS gene expressi
on.