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首页> 外文期刊>American Journal of Physiology >Rosiglitazone improves aortic arginine transport, through inhibition of PKCa, in uremic rats
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Rosiglitazone improves aortic arginine transport, through inhibition of PKCa, in uremic rats

机译：罗格列酮通过抑制PKCa改善尿毒症大鼠的主动脉精氨酸转运

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First published June 4, 2008; doi:10.1152/ajprenal.00619.2007.-Peroxisome prolif-erator-activated receptor (PPAR) agonists were shown to inhibit atherosclerosis through augmentation of endothelial nitric oxide synthase (eNOS) activity. In addition, rosiglitazone exerts a beneficial effect in chronic renal failure (CRF). Since L-arginine transport by CAT-1 (the specific arginine transporter for eNOS) is inhibited in uremia, we aimed to explore the effect of rosiglitazone on arginine transport in CRF. Arginine uptake by aortic rings was studied in control animals, rats, 6 wk following 5/6 nephrectomy (CRF) and rats with CRF treated with rosiglitazone. The decrease of arginine transport in CRF was prevented by rosiglitazone. Immunobloting revealed that CAT-1 protein was decreased in CRF but remained unchanged following rosiglitazone administration. Protein content of the membrane fraction of PKCa and phosphorylated CAT-1 increased significantly in CRF, effects that were prevented by rosiglitazone. PKCa phosphorylation was unchanged but significantly attenuated by rosiglitazone in CRF. Ex vivo administration of phorbol-12-myristate-13-acetate to rosiglitazone-treated CRF rats significantly attenuated the effect of rosiglitazone on arginine uptake. The decrease in cGMP response to carbamyl-choline (eNOS agonist) was significantly attenuated by rosiglitazone in CRF. Western blotting and immunohisto-chemistry analysis revealed that protein nitration was intensified in the endothelium of CRF rats and this was attenuated by rosiglitazone. In conclusion, rosiglitazone prevents the decrease in arginine uptake in CRF through both depletion and inactivation of PKCa. These findings are associated with restoration of eNO generation and attenuation of protein nitration and therefore may serve as a novel mechanism to explain the beneficial effects of rosiglitazone on endothelial function in uremia.
机译：首次发布于2008年6月4日; doi：10.1152 / ajprenal.00619.2007.-过氧化物酶体增生因子激活受体（PPAR）激动剂通过增强内皮一氧化氮合酶（eNOS）活性抑制动脉粥样硬化。此外，罗格列酮在慢性肾功能衰竭（CRF）中发挥有益作用。由于尿毒症抑制了CAT-1的L-精氨酸转运（eNOS的特定精氨酸转运蛋白），因此我们旨在探讨罗格列酮对CRF中精氨酸转运的影响。在对照动物，大鼠，5/6肾切除术（CRF）后6周和罗格列酮治疗的CRF大鼠中研究了主动脉环对精氨酸的摄取。罗格列酮阻止了CRF中精氨酸转运的减少。免疫印迹显示，在服用罗格列酮后，CRF中的CAT-1蛋白下降，但保持不变。罗格列酮可防止CRF中PKCa和磷酸化CAT-1膜部分的蛋白质含量显着增加。 PKCa磷酸化未改变，但在CRF中被罗格列酮显着减弱。向罗格列酮治疗的CRF大鼠离体给予phorbol-12-肉豆蔻酸酯13-乙酸酯显着减弱了罗格列酮对精氨酸摄取的影响。罗格列酮在CRF中显着减弱了对氨甲胆碱（eNOS激动剂）的cGMP反应的降低。蛋白质印迹和免疫组织化学分析显示，CRF大鼠内皮中的蛋白质硝化作用增强，并且被罗格列酮减弱。总之，罗格列酮可通过PKCa的消耗和失活防止CRF中精氨酸摄入的减少。这些发现与eNO生成的恢复和蛋白硝化的减弱有关，因此可作为解释罗格列酮对尿毒症内皮功能的有益作用的新机制。

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