Abstract
The present experiments were designed to assess a possible role of H2O2 in the proliferation of cultured rat mesangial cells, as well as to evaluate the effect of different calcium channel blockers and a platelet-activating factor antagonist on this proliferation. Cultured rat mesangial cells were plated at two densities (10,000 and 25,000 cells/well) in 24-well dishes, and proliferation was measured by analyzing [3H]thymidine incorporation and by directly counting the cells. Hydrogen peroxide, 100 microM, increased [3H]thymidine incorporation at the two densities tested (85 and 59%, respectively), as well as the number of cells (53 and 23%, respectively). This effect was dose dependent and it was blocked completely by verapamil and diltiazem, 10 microM, but not by TMB-8 [3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester] at the same concentration. BN 52021, a competitive antagonist of platelet-activating factor, only slightly blocked the H2O2-dependent proliferation. The inhibitory action of the two calcium antagonists tested started at concentrations as low as 1 nM, and inhibited completely the H2O2 stimulated proliferation at concentrations between 0.1 and 1 microM. These results establish that H2O2 is able to induce proliferation of mesangial cells. Although the pathophysiological implications of this finding remain to be proven, these data suggest a potential therapeutic action of calcium antagonist in inflammatory conditions such as glomerulonephritis.
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