Journal article
Sphingosine reverses growth inhibition caused by activation of protein kinase c in vascular smooth muscle cells
Journal of cellular physiology, Vol.149(2), pp.307-312
11/1991
DOI: 10.1002/jcp.1041490218
PMID: 1748721
Abstract
In certain cell systems, including neonatal vascular smooth muscle (VSM) cells, phorbol esters are growth inhibitory. Here we show that 1, 2-dioctanoyl-snglycerol (DiC8), when added 2 h after α-thrombin, reverses by 95% the induction of DNA synthesis in VSM cells by α-thrombin. Sphingosine, a naturally occurring lysosphingolipid inhibitor of protein kinase C, and its synthetic analogues N-acetylsphingosine and C11-sphingosine were used to investigate this phenomenon further. Neither phorbol 12-myristate 13-acetate (PMA;200 ng/ml) nor sphingosine (up to 10 μM) alone had any effect upon basal DNA synthesis in VSM cells. Like DiC8, PMA totally blocked the induction of DNA synthesis by α-thrombin. This inhibitory effect of PMA was reversed by sphingosine in a dose-dependent manner with complete reversal at 10 μM. Neither N-acetylsphingosine nor C11-sphingosine exhibited any effect on DNA synthesis in VSM cells. The effect of sphingosine and its analogues on the activity of protein kinase C extracted from VSM cells was measured by histone III-S phosphorylation. Protein kinase C activity was inhibited 50% by 300 μM sphingosine, but 15% by similar concentrations of N-acetylsphingosine and C11-sphingosine. To assess the effects of sphingosine and analogues on protein kinase C in intact cells, we examined the effect of the lipids on [3H]phorbol dibutyrate binding. Sphingosine (at > 5 μM), but not N-acetylsphingosine or C11-sphingosine, blocked [3H]phorbol dibutyrate binding in a dose- and time-dependent fashion. Thus the mechanism of growth inhibition by DiC8 and PMA in neonatal VSM cells appears to be through activation of protein kinase C by these compounds. Sphingosine reverses this growth inhibition through interference with the binding to protein kinase C of phorbol esters or other activators of this enzyme.
Details
- Title: Subtitle
- Sphingosine reverses growth inhibition caused by activation of protein kinase c in vascular smooth muscle cells
- Creators
- Robert H Weiss - Division of Nephrology, Cardiovascular Research Institute, University of California, San Francisco, California 94143Chou-Long Huang - Division of Nephrology, Cardiovascular Research Institute, University of California, San Francisco, California 94143Harlan E Ives - Division of Nephrology, Cardiovascular Research Institute, University of California, San Francisco, California 94143
- Resource Type
- Journal article
- Publication Details
- Journal of cellular physiology, Vol.149(2), pp.307-312
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- DOI
- 10.1002/jcp.1041490218
- PMID
- 1748721
- ISSN
- 0021-9541
- eISSN
- 1097-4652
- Number of pages
- 6
- Language
- English
- Date published
- 11/1991
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094767702771
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