Laboratory of Immune Cell Biology, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.
Apoptosis. 2011 Feb;16(2):162-73. doi: 10.1007/s10495-010-0556-y.
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.
形成脉管系统的细胞采用不同的机制来抵消细胞因子和血液中细胞暴露的有害后果。血管稳态部分依赖于基因，这些基因的表达在这些细胞中受到血流动力的影响而增加。PP1201（也称为 RECS1）就是这样一种基因，其表达水平在受到层流剪切力时增加。缺乏 PP1201 的老年小鼠易发生囊性中膜变性（CMD），这是一种主动脉瘤的形式，表现为平滑肌细胞丢失和嗜碱性物质堆积。在这里，我们发现较高水平的 PP1201 可以防止 Fas 配体（FasL）诱导的细胞凋亡。PP1201 与 Fas 受体（CD95/Apo1）相互作用，并在高尔基区室中与它共定位。与同源物 lifeguard（LFG）不同，在几种类型的细胞中包括原代人主动脉平滑肌细胞（AoSMC）中过表达 PP1201 不会改变 Fas 的总水平，而只会降低质膜上 Fas 的表达。只有高但不是组成型的 PP1201 水平控制 Fas 信号。我们的数据表明，PP1201 作为一种抗凋亡蛋白发挥作用，其在血管细胞中的表达增加可以通过减少 Fas 向质膜的运输来促进稳态。
