The heat-shock transcription factor HSF1 is rapidly activated by either hyper- or hypo-osmotic stress in mammalian cells
The heat-shock transcription factor HSF1 is rapidly activated by either hyper- or hypo-osmotic stress in mammalian cells
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DOI：
10.1042/bj3270341
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发表时间：
1997-10-15
影响因子：
4.1
通讯作者：
Chen, KY
中科院分区：
文献类型：
--
作者：
Caruccio, L;Bae, SW;Chen, KY
渗透调节是细胞对环境渗透压和离子强度变化的反应，对生物体的生存至关重要。我们以前已经证明，哺乳动物细胞暴露于低渗胁迫，无论是在生长培养基（30%生长培养基和70%水）中还是在含有山梨醇和水的二元溶液中，都显著诱导热休克转录因子（HSF 1）的DNA结合活性[Huang，Caruccio，Liu和Chen（1995）Biochem.J.307，347-352]。由于高渗和低渗应激通常引起相反的生物学反应，我们想知道高渗应激对HSF激活的影响。在这项研究中，我们已经研究了HSF DNA结合活性的HeLa细胞保持在山梨醇/水二元溶液在一个较宽的浓度范围（0.1-0.9M），并在Dulbecco的培养基中补充山梨醇或NaCl。我们发现，在低渗（0.1-0.25 M）和高渗（0.50-0.90 M）条件下均可显著诱导HSF结合活性。在这两种情况下，HSF激活后5分钟内观察到改变渗透压。该活化伴随着HSF三聚化和核转位，并且似乎独立于蛋白质合成。一旦细胞恢复到等渗条件（0.30 M），低渗或高渗胁迫对HSF活化的影响可以逆转，半衰期（t（1/2））为25 min或更短。与热休克不同，无论是低或高渗应激激活HSF并不导致HeLa细胞中的热休克蛋白70（HSP 70）mRNA的积累。我们建议，HSF激活渗透胁迫期间可能独立的热休克蛋白的合成的生理功能。
Osmoregulation, the cellular response to environmental changes of osmolarity and ionic strength, is important for the survival of living organisms. We have demonstrated previously that an exposure of mammalian cells to hypo-osmotic stress, either in growth medium (30% growth medium and 70% water) or in binary solution containing sorbitol and water, prominently induced the DNA-binding activity of the heat-shock transcription factor (HSF1) [Huang, Caruccio, Liu and Chen (1995) Biochem. J. 307, 347-352]. Since hyperosmotic and hypo-osmotic stress usually elicit opposite biological responses, we wondered what would be the effect of hyperosmotic stress on HSF activation. In this study we have examined the HSF DNA-binding activity in HeLa cells maintained in the sorbitol/water binary solution over a wide concentration range (0.1-0.9M) and in Dulbecco's medium supplemented with sorbitol or NaCl. We found that HSF-binding activity could be induced prominently under both hypo-osmotic (0.1-0.25 M) and hyperosmotic conditions (0.50-0.90 M). In both cases, HSF activation was observed within 5 min after changing the osmotic pressure. The activation was accompanied by both HSF trimerization and nuclear translocation, and appeared to be independent of protein synthesis. The effects of hypo-or hyper-osmotic stress on HSF activation could be reversed once the cells were returned to iso-osmotic conditions (0.30 M) with a half-life (t(1/2) of 25 min or less. This rapid turnover of the osmotic-stress-induced HSF-binding activity was inhibited by cycloheximide, a potent inhibitor of protein synthesis. Unlike heat shock, activation of HSF by either hypo-or hyper-osmotic stress did not lead to an accumulation of heat-shock protein 70 (HSP70) mRNA in HeLa cells. We propose that HSF activation during osmotic stress may serve physiological functions independent of the synthesis of heat-shock proteins.