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首页> 外文期刊>Apoptosis >A shear stress responsive gene product PP1201 protects against Fas-mediated apoptosis by reducing Fas expression on the cell surface
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A shear stress responsive gene product PP1201 protects against Fas-mediated apoptosis by reducing Fas expression on the cell surface

机译：剪应力响应基因产物PP1201通过减少细胞表面的Fas表达来防止Fas介导的细胞凋亡

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摘要

Cells that form vascular system employ different mechanisms to offset deleterious consequences of exposure to cytokines and cells present in blood. Vascular homeostasis is sustained in part by genes, whose expression increases in response to hemodynamic forces in these cells. PP1201 (also known as RECS1) is one such gene whose expression level increases in response to laminar shear stress. Aged mice deficient in PP1201 are prone to develop cystic medial degeneration (CMD), a form of aortic aneurism manifested with loss of smooth muscle cells and accumulation of basophilic substances. Here we found that higher levels of PP1201 can protect against Fas ligand (FasL)-induced apoptosis. PP1201 interacted with the Fas receptor (CD95/Apo1) and colocalized with it in the Golgi compartment. Unlike its homolog lifeguard (LFG), PP1201 overexpression in several types of cells including primary human aortic smooth muscle cells (AoSMC) decreased the expression of Fas on the plasma membrane without changing the total Fas levels. Only high but not constitutive level of PP1201 controls Fas signaling. Our data suggest that PP1201 functions as an anti-apoptotic protein and its increased expression in vascular cells can contribute to homeostasis by reducing Fas trafficking to the cell membrane.
机译：形成血管系统的细胞采用不同的机制来抵消暴露于血液中存在的细胞因子和细胞的有害后果。血管稳态部分地由基因维持，这些基因的表达响应于这些细胞中的血液动力而增加。 PP1201（也称为RECS1）就是这样一种基因，其表达水平响应层流剪切应力而增加。缺乏PP1201的老年小鼠易于发展为囊性内侧变性（CMD），这是一种主动脉动脉瘤，表现为平滑肌细胞丢失和嗜碱性物质积累。在这里，我们发现更高水平的PP1201可以抵抗Fas配体（FasL）诱导的细胞凋亡。 PP1201与Fas受体（CD95 / Apo1）相互作用，并在高尔基体中共定位。不同于其同系物救生员（LFG），PP1201在包括原代人主动脉平滑肌细胞（AoSMC）在内的几种类型细胞中的过表达降低了质膜上Fas的表达，而没有改变总Fas水平。 PP1201仅高水平而非组成型水平控制Fas信号传导。我们的数据表明PP1201作为一种抗凋亡蛋白，其在血管细胞中的表达增加可以通过减少Fas转运到细胞膜来促进体内稳态。

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