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Role of calcium in gentamicin-induced mesangial cell activation

机译:钙在庆大霉素诱导的系膜细胞活化中的作用

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Gentamicin-induced decreases in glomerular filtration rate have been associated to a marked decline in the glomerular capillary ultrafiltration coefficient which could be due to an active contraction of mesangial cells. In the present work we assessed a possible role of cytosolic Ca2+ as a mediator that leads to contraction and proliferation induced by gentamicin on mesangial cells. Gentamicin (10(-5)M) induced an increase in cytosolic free Ca2+, that was fully inhibited by the calcium channel blocker, verapamil, and by the endoplasmic reticulum calcium release blocker, TMB-8. Gentamicin induced a planar surface area reduction in cultured mesangial cells, that was blunted by verapamil and TMB-8. Gentamicin also stimulated [H-3]thymidine incorporation into DNA and increased viable cell number, effects that were reduced by both, verapamil and TMB-8. Gentamicin stimulated the expression of the AP1 protein; this expression was partially blunted by verapamil and TMB-8. Moreover, verapamil inhibited gentamicin-induced PAF synthesis from mesangial cells. in summary, gentamicin directly raised intracellular Ca2+ activating both calcium influx from external medium and calcium release from internal stores. This increase is responsible of cellular activation (contraction and proliferation) and PAF synthesis induced by gentamicin on mesangial cells. Copyright (C) 2000 S. Karger AG, Basel. [References: 26]
机译:庆大霉素诱导的肾小球滤过率降低与肾小球毛细血管超滤系数的明显下降有关,这可能是由于肾小球系膜细胞的主动收缩所致。在目前的工作中,我们评估了胞质Ca2 +作为介导庆大霉素在系膜细胞上诱导的收缩和增殖的介质的可能作用。庆大霉素(10(-5)M)诱导细胞内游离Ca2 +的增加,该增加被钙通道阻滞剂维拉帕米和内质网钙释放阻滞剂TMB-8完全抑制。庆大霉素诱导培养的系膜细胞的平面表面积减少,这被维拉帕米和TMB-8抑制。庆大霉素还刺激[H-3]胸苷掺入DNA并增加活细胞数量,维拉帕米和TMB-8均降低了作用。庆大霉素刺激AP1蛋白的表达;该表达部分被维拉帕米和TMB-8钝化。此外,维拉帕米抑制了庆大霉素诱导的系膜细胞合成PAF。总而言之,庆大霉素直接提高细胞内Ca2 +的浓度,从而激活了来自外部介质的钙流入和内部存储的钙释放。这种增加与庆大霉素在系膜细胞上诱导的细胞活化(收缩和增殖)和PAF合成有关。版权所有(C)2000 S.Karger AG,巴塞尔。 [参考:26]

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