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吡格列酮经PPARγ/ERK通路刺激胚胎成纤维细胞钠氢交换子的转运

Pioglitazone stimulates Na^+/H^+ exchanger 1 (NHE1) transfer by PPARγ/ERK pathway in the mice embryonic fibroblast cells
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摘要 目的研究吡格列酮对钠氢离子转运体(NHE1)的转运作用及传导通路,探讨噻唑烷二酮类药物引起水肿的机制。方法野生及PPARγ^(-/-)鼠胚胎成纤维细胞分为:对照组(DMEM培养液),ERK抑制剂(10μmol/L PD98059)组,PPARγ拮抗剂(5μmol/L GW9662)组,基因转录抑制剂(5μmol/LActiomycin D)组。测定各组细胞在0.3μmol/L吡格列酮灌注下NHE1的活性,Western blot法测定ERK磷酸化。结果吡格列酮增加野生鼠NHE1活性48.1%±3.1%,其作用被ERK抑制剂及PPARγ拮抗剂阻止,而不被基因转录抑制剂阻止;吡格列酮刺激野生鼠ERK磷酸化,对PPARγ^(-/-)鼠无此作用。结论吡格列酮经PPARγ/ERK通路,不依赖基因转录,刺激鼠胚胎成纤维细胞NHE1的转运,促进钠潴留。 Objective To investigate the effect and pathway of Pioglitazone on NHE1 transfer in mice embryonic fibroblast (EF) cells, and to realize the underlying mechanism of edema induced by thiazolidinediones. Methods Embryonic fibroblast cells from wild-type and PPARγ -/-mice were divided into four groups: control, ERK inhibitor PD98059 (10μmol/L), PPAR-γ inhibitor GW9662 (5μmol/L) and gene transfer inhibitor actiomycin D (ACD 5μmol/L) groups. NHE1 activity was determined by pHi change after the intracellular acidosis. NHE1 activity of each group was measured after 0.3μmol/L pioglitazone transfusion. ERK activation of EF cells from wild-type and PPARγ-/- mice were detected by Western blot. Results Pioglitazon stimulated NHE1 transfer activity in wild type EF cells by 48.1%±3.1% but not in PPARγ-/- mice. This stimulation was inhibited by ERK inhibitor and PPARγ inhibitor but not by gene transfer inhibitor. The 0.3μmol/L pioglitazone stimulated ERK activation only in EF cells from wild type not in PPARγ-/- cells. Conclusions Pioglitazone stimulates NHE1 activity by PPARγ/ERK pathway through non-genomic mechanism, and this is most likely responsible for the edema induced by TZDs.
作者 李月红 王梅
出处 《中国糖尿病杂志》 CAS CSCD 北大核心 2010年第9期692-695,共4页 Chinese Journal of Diabetes
基金 教育部回国人员启动基金(F001 806001)
关键词 吡格列酮 过氧化物酶体增殖物活化受体 细胞外信号调节激酶 胚胎成纤维细胞 Na^+/H^+离子转运体 Pioglitazone Peroxisome proliferator activated receptors Extracellular signal-regulated protein kinase Embryonic fibroblast cells Na+/H+ cotransporter 1
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