Epoxyeicosatrienoic acids activate Na+/H+ exchange and are mitogenic in cultured rat glomerular mesangial cells
✍ Scribed by R. C. Harris; H. R. Jacobson; J. Capdevila; T. Homma
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 893 KB
- Volume
- 144
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
The present slucly exdrninetl responses of cultured rat glomerular mesangial cells to exogerious exposure of epoxyeicosatrienoic acids (LET'S), products of cytochrome P450 epoxygenase. One day after administration of 8,9or I4;l S-EET, cultured rat rnesangial cells denionstratecl significant incrcases in I'HIthymidine incorporation (10 ' M I4,13-EET: '120+7')/0 otcontrol; n=6; P<0.025; lo-'' M 14,15-EET: 1451lO%; n-20; P<0.0005; IO-" M 8.Y-EET: 167-t31%; n=9; t'85% of .3 inM "Na uptake into mesangial cellswas inhibited by I m M drniloricle, indicating N a f / H C exchangc. Uticlcr these conditions, I4,15-CCT stimulated Nd+/l I + exchange by 42% and 8,Y-EE.1-stimulated N a + l H + exchangc by 59%. Neither protein kinase C depletion nor addition oi the protein kinase C inhibitor, staurosporinc, affcctcd this stimulation. lii I 'Hlniyo-inositol loaded mesangial cells, no significant stimulation of ptiosphoinositidr hydrolysis m s detected in response to administration of 14,15-EET.
Twenty-four hours after addition of I"(Cj14,15-EET, >90% was prelerentially esterified to c e l l ~~l a r lipids, with preclorninant incorporation into phosphatidylinositol, phosphatidylethanolamine, and diacylglycerol.
Thus, these results demonstrate epoxyeicosatrienoic acids stimulate Na+/H + exchange and mitogcncsis in mesangial cells. These ellects do not jppear to be