Hyperthermia induces the ER stress pathway.
Hyperthermia induces the ER stress pathway.
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DOI：
10.1371/journal.pone.0023740
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Cavener DR
中科院分区：
文献类型：
--
作者：
Xu X;Gupta S;Hu W;McGrath BC;Cavener DR
内质网伴侣GRP78/BiP是热休克蛋白Hsp70家族的同源物，但GRP78/BiP不是由热休克诱导的，而是由内质网应激诱导的。然而，以前的研究并没有考虑到与热性热疗相关的生理相关的温度升高。在本报告中，我们研究了暴露于40°C的细胞中GRP78/BiP和内质网应激途径的其他组分的反应。将AD293细胞暴露于43°C热休克中，以证实内质网应激反应基因的抑制作用。将包括AD293细胞在内的五种哺乳动物细胞类型暴露于40°C高温下不同时间，并评估内质网应激途径的诱导情况。热休克（43°C）对内质网应激途径的抑制作用得到证实。相比之下，受到更温和的温度升高（40°C）的细胞表现出部分或完全内质网应激途径诱导，这是由内质网应激途径三个臂的下游目标以及热休克反应决定的。缺乏Perk或Gcn2的细胞对高温引起的内质网应激表现出极大的敏感性。内质网应激途径在热疗诱导Hsp70的同时部分或全部被诱导。这些发现表明，内质网和细胞质包含平行通路，以协调调节对与疾病或感染相关的发热性高温的适应。
The ER chaperone GRP78/BiP is a homolog of the Hsp70 family of heat shock proteins, yet GRP78/BiP is not induced by heat shock but instead by ER stress. However, previous studies had not considered more physiologically relevant temperature elevation associated with febrile hyperthermia. In this report we examine the response of GRP78/BiP and other components of the ER stress pathway in cells exposed to 40°C. AD293 cells were exposed to 43°C heat shock to confirm inhibition of the ER stress response genes. Five mammalian cell types, including AD293 cells, were then exposed to 40°C hyperthermia for various time periods and induction of the ER stress pathway was assessed. The inhibition of the ER stress pathway by heat shock (43°C) was confirmed. In contrast cells subjected to more mild temperature elevation (40°C) showed either a partial or full ER stress pathway induction as determined by downstream targets of the three arms of the ER stress pathway as well as a heat shock response. Cells deficient for Perk or Gcn2 exhibit great sensitivity to ER stress induction by hyperthermia. The ER stress pathway is induced partially or fully as a consequence of hyperthermia in parallel with induction of Hsp70. These findings suggest that the ER and cytoplasm of cells contain parallel pathways to coordinately regulate adaptation to febrile hyperthermia associated with disease or infection.
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DOI：
10.1073/pnas.84.3.680
发表时间：
1987-02-01
影响因子：
11.1
作者：
CHANG, SC;WOODEN, SK;LEE, AS
通讯作者：
LEE, AS
影响因子：
3.1
作者：
IKEGUCHI, M;TEETER, LD;KUO, MT
通讯作者：
KUO, MT
影响因子：
7.7
作者：
Gupta S;McGrath B;Cavener DR
通讯作者：
Cavener DR
DOI：
10.1083/jcb.153.5.1011
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Novoa I;Zeng H;Harding HP;Ron D
通讯作者：
Ron D
影响因子：
3.8
作者：
GRAHAM, FL;SMILEY, J;NAIRN, R
通讯作者：
NAIRN, R