Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells
Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells
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DOI：
10.1016/j.yexcr.2008.07.001
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发表时间：
2008-10-01
影响因子：
3.7
通讯作者：
Akiyama, Shin-ichi
中科院分区：
文献类型：
--
作者：
Ikeda, Ryuji;Iwashita, Ken-ichi;Akiyama, Shin-ichi
主要穹窿蛋白 (MVP) 是穹窿颗粒的主要成分，是迄今为止描述的最大的核糖核蛋白复合物，与肺阻力相关蛋白 (LRP) 相同。尽管 MVP 也在多种正常组织中表达，但对其生理作用知之甚少。 MVP 对某些外源物质和其他压力发挥了保护作用。因此，我们通过用蔗糖或 NaCl 处理人结肠癌 SW620 细胞，研究了渗透压对 MVP 表达的影响。 MVP 蛋白和 MVP mRNA 的表达水平均因渗透压而增加。蔗糖或氯化钠也可以增强 MVP 启动子活性。 SB203580 抑制 SW620 细胞中的 p38 MAPK 可抑制高渗应激下 MVP 的表达。这些发现表明渗透压通过 p38 MAPK 途径上调 MVP 的表达。 SW620 细胞中 MVP 干扰 RNA (RNAi) 下调 MVP 表达增加了细胞对高渗应激的敏感性并增强了细胞凋亡。此外，MVP RNAi 阻止了渗透压诱导的磷酸化 Akt 的时间依赖性增加。这些发现表明 PI3K/Akt 通路可能与 MVP 的细胞保护作用有关。我们的数据表明，细胞暴露于高渗应激会诱导 MVP，这可能在保护细胞免受渗透应激的不利影响方面发挥重要作用。 (C) 2008 Elsevier Inc. 保留所有权利。
The major vault protein (MVP) is the major constituent of the vault particle, the largest ribonuclear protein complex described to date and is identical to lung resistance-related protein (LRP). Although MVP is also expressed in several normal tissues, little is known about its physiological role. MVP played a protective role against some xenobiotics and other stresses. We thus investigated the effect of osmotic stress on MVP expression by treating human colon cancer SW620 cells with sucrose or NaCl. The expression level of both MVP protein and MVP mRNA was increased by the osmostress. Sucrose or sodium chloride could also enhance MVP promoter activity. Inhibition of p38 MAPK in SW620 cells by SB203580 inhibited the expression of MVP under hyperosmotic stress. These findings suggested that osmotic stress up-regulated the MVP expression through p38 MAPK pathway. Down-regulation of MVP expression by MVP interfering RNA (RNAi) in SW620 cells increased the sensitivity of the cells to hyperosmotic stress and enhanced apoptosis. Furthermore, MVP RNAi prevented the osmotic stress-induced, time-dependent increase in phosphorylated Akt. These findings suggest that the PI3K/Akt pathway might be implicated in the cytoprotective effect of MVP.Our data demonstrate that exposure of cells to hyperosmotic stress induces MVP that might play an important role in the protection of the cells from the adverse effects of osmotic stress. (C) 2008 Elsevier Inc. All rights reserved.