Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes.
Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes.
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DOI：
10.1016/j.yexcr.2012.03.011
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发表时间：
2012-06-10
影响因子：
3.7
通讯作者：
Miller, R. Tyler
中科院分区：
文献类型：
--
作者：
Huang, Chunfa;Bruggeman, Leslie A.;Hydo, Lindsey M.;Miller, R. Tyler
由内皮细胞、肾小球基底膜和足细胞组成的肾小球毛细血管壁持续地经受由血压引起的牵拉应力和血流引起的剪切应力引起的血液动力学力。肾小球暴露于异常的血流动力学力量，如超滤与肾小球损伤和进行性肾脏疾病，并在该过程的调节机械刺激的化学信号的转换知之甚少足细胞。通过检测DNA片段化、凋亡细胞核的变化和细胞色素c的释放，我们发现切应力诱导足细胞凋亡。同时，足细胞暴露于剪切应力也刺激c-Src磷酸化，磷脂酶D（PLD）激活和哺乳动物雷帕霉素靶（mTOR）信号。使用c-Src，PLD 1，和PLD 2的抗体进行相互免疫共沉淀和体外PLD活性测定，我们的数据表明，c-Src相互作用，并激活PLD 1，而不是PLD 2。PP 2（c-Src激酶的特异性抑制剂）抑制剪切应力诱导的c-Src磷酸化导致PLD活性降低。剪切应力诱导PLD激活产生的磷脂酸刺激mTOR信号，并引起足细胞肥大和凋亡。
The glomerular capillary wall, composed of endothelial cells, the glomerular basement membrane and the podocytes, is continually subjected to hemodynamic force arising from tractional stress due to blood pressure and shear stress due to blood flow. Exposure of glomeruli to abnormal hemodynamic force such as hyperfiltration is associated with glomerular injury and progressive renal disease, and the conversion of mechanical stimuli to chemical signals in the regulation of the process is poorly understood in podocytes. By examining DNA fragmentation, apoptotic nuclear changes and cytochrome c release, we found that shear stress induced cell apoptosis in cultured podocytes. Meanwhile, podocytes exposed to shear stress also stimulated c-Src phosphorylation, phospholipase D (PLD) activation and mammalian target of rapamycin (mTOR) signaling. Using the antibodies against c-Src, PLD1, and PLD2 to perform reciprocal co-immunoprecipitations and in vitro PLD activity assay, our data indicated that c-Src interacted with and activated PLD1 but not PLD2. The inhibition of shear stress-induced c-Src phosphorylation by PP2 (a specific inhibitor of c-Src kinase) resulted in reduced PLD activity. Phosphatidic acid, produced by shear stress-induced PLD activation, stimulated mTOR signaling, and caused podocyte hypertrophy and apoptosis.
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影响因子：
2.5
作者：
Kriz, W
通讯作者：
Kriz, W
影响因子：
8.3
作者：
Boulanger, Chantal M.;Amabile, Nicolas;London, Gerard M.
通讯作者：
London, Gerard M.
影响因子：
56.9
作者：
Fang, YM;Vilella-Bach, M;Chen, J
通讯作者：
Chen, J
DOI：
10.1152/ajpheart.01047.2006
发表时间：
2007-03-01
影响因子：
4.8
作者：
Chien, Shu
通讯作者：
Chien, Shu
影响因子：
19.6
作者：
Durvasula, RV;Petermann, AT;Shankland, SJ
通讯作者：
Shankland, SJ