Systemic analysis of heat shock response induced by heat shock and a proteasome inhibitor MG132.
Systemic analysis of heat shock response induced by heat shock and a proteasome inhibitor MG132.
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DOI：
10.1371/journal.pone.0020252
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lee KJ
中科院分区：
文献类型：
--
作者：
Kim HJ;Joo HJ;Kim YH;Ahn S;Chang J;Hwang KB;Lee DH;Lee KJ
热休克反应(HSR)是一种抵抗各种压力的细胞防御机制，其分子基础尚不清楚。在这项研究中，我们首次全面分析了热休克和蛋白酶体抑制剂MG132(这两种物质都能诱导热休克蛋白)引起的基因表达变化，比较了正常小鼠纤维肉瘤细胞系RIF-1及其耐热变异体细胞系TR-RIF-1(TR)对这两种应激反应的反应。我们研究的细胞反应包括热休克蛋白的表达、细胞活力、总蛋白合成模式和多泛素化蛋白的积累。我们还使用微阵列分析比较了暴露在两种压力下的两种细胞系的mRNA表达谱和动力学。与RIF-1细胞相比，TR细胞抵抗热休克引起的细胞活力和全细胞蛋白质合成的变化。两种细胞系的总细胞蛋白合成和多泛素化蛋白的积累模式是不同的，这取决于压力和细胞系。基因芯片分析表明，在热休克条件下，TR细胞的基因表达模式比RIF-1细胞更快、更短暂，而RIF-1细胞和TR细胞对MG132的反应表现出相似的基因表达动力学。我们还发现2,208个基因上调2倍以上，可将其分为三类：1)受热休克和MG132共同调控的基因(如伴侣)；2)仅受热休克调控的基因(如DNA结合蛋白，包括组蛋白)；以及3)仅受MG132调控的基因(如先天免疫和防御相关分子)。本研究表明，热激和MG132在某些方面具有HSR信号通路的共同点，同时诱导不同的应激反应信号通路，由不同的异常蛋白触发。
The molecular basis of heat shock response (HSR), a cellular defense mechanism against various stresses, is not well understood. In this, the first comprehensive analysis of gene expression changes in response to heat shock and MG132 (a proteasome inhibitor), both of which are known to induce heat shock proteins (Hsps), we compared the responses of normal mouse fibrosarcoma cell line, RIF- 1, and its thermotolerant variant cell line, TR-RIF-1 (TR), to the two stresses. The cellular responses we examined included Hsp expressions, cell viability, total protein synthesis patterns, and accumulation of poly-ubiquitinated proteins. We also compared the mRNA expression profiles and kinetics, in the two cell lines exposed to the two stresses, using microarray analysis. In contrast to RIF-1 cells, TR cells resist heat shock caused changes in cell viability and whole-cell protein synthesis. The patterns of total cellular protein synthesis and accumulation of poly-ubiquitinated proteins in the two cell lines were distinct, depending on the stress and the cell line. Microarray analysis revealed that the gene expression pattern of TR cells was faster and more transient than that of RIF-1 cells, in response to heat shock, while both RIF-1 and TR cells showed similar kinetics of mRNA expression in response to MG132. We also found that 2,208 genes were up-regulated more than 2 fold and could sort them into three groups: 1) genes regulated by both heat shock and MG132, (e.g. chaperones); 2) those regulated only by heat shock (e.g. DNA binding proteins including histones); and 3) those regulated only by MG132 (e.g. innate immunity and defense related molecules). This study shows that heat shock and MG132 share some aspects of HSR signaling pathway, at the same time, inducing distinct stress response signaling pathways, triggered by distinct abnormal proteins.
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影响因子：
3.5
作者：
Kaspari, Marion;Tavalai, Nina;Bogner, Elke
通讯作者：
Bogner, Elke
影响因子：
5.2
作者：
Hungness, ES;Robb, BW;Hasselgren, PO
通讯作者：
Hasselgren, PO
影响因子：
5.4
作者：
Harty, RN;Brown, ME;Schnell, MJ
通讯作者：
Schnell, MJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.5
作者：
Khor, R;McElroy, LJ;Whittaker, GR
通讯作者：
Whittaker, GR