TAILIEUCHUNG - Báo cáo khóa học: Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump Robert Saunders and Georgios Scheiner-Bobis

Ouabain, a sodiumpump (Na + /K + -ATPase) inhibitor, has been shown to act as a hormone and is possibly involved in the pathogenesis of hypertension. The mechanismby which ouabain may act was investigated using primary cultures of human umbilical artery endothelial cells (HUAECs), which are known to express and release the vasoconstrictive hor-mone endothelin (ET-1). Fiveminutes after application, low concentrations of ouabain induced Ca 2+ oscillations and stimulated ET-1 release from endothelial cells into the medium. To investigate whether the observed effects were due to inhibition of the sodiumpump, the effects of ouabain on the uptake of 86 Rb + by HUAECs were examined | Eur. J. Biochem. 271 1054-1062 2004 FEBS 2004 doi Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump Robert Saunders and Georgios Scheiner-Bobis Institut fur Biochemie und Endokrinologie Fachbereich Veterinarmedizin Justus-Liebig-Universitdt Giessen Germany Ouabain a sodium pump Na K -ATPase inhibitor has been shown to act as a hormone and is possibly involved in the pathogenesis of hypertension. The mechanism by which ouabain may act was investigated using primary cultures of human umbilical artery endothelial cells HUAECs which are known to express and release the vasoconstrictive hormone endothelin ET-1 . Five minutes after application low concentrations of ouabain induced Ca2 oscillations and stimulated ET-1 release from endothelial cells into the medium. To investigate whether the observed effects were due to inhibition of the sodium pump the effects of ouabain on the uptake of 86Rb by HUAECs were examined. Unexpectedly ouabain concentrations below 10 nM stimulated 86Rb uptake by 15-20 and in some experiments by 50 results that are consistent with a stimulation of the pump. Within the concentration range 1-10 nM ouabain induced a stimulation phosphorylation of mitogen-activated protein kinase MAP kinase . After incubation of HUAECs with ouabain for 12 h the glycoside stimulated cell growth by 49 4 as measured by cell number with a maximum response at 5 nM. At similar concentrations ouabain also increased ET-1 mRNA abundance by . The results indicate that by influ-encingET-1 expression and release ouabain may contribute to the regulation of vascular tone. The data also confirm that it is not a global inhibition of the sodium pump that is involved in the mechanism of action of this cardiac glycoside. Keywords endothelin human umbilical cord endothelial cell HUAEC mitogen-activated protein kinase MAP kinase sodium pump ouabain. Na K -ATPase the .

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