Jeong J K, Huang Q, Lau S S, Monks T J
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, USA.
J Biol Chem. 1997 Mar 14;272(11):7511-8. doi: 10.1074/jbc.272.11.7511.
Cells respond to a variety of stresses by activating the transcription of a battery of "acute phase" or "stress response" genes. The nature of this response is tailored to the nature of the stress. The extent to which physiologically and pathophysiologically induced growth arrest share common genomic responses is unclear. We therefore compared the effects of a physiologically induced (serum and nutrient depletion) and a chemically induced (2-Br-bis-(GSyl)HQ and 2-Br-6-(GSyl)HQ) stress in renal tubular epithelial cells (LLC-PK1). The response to physiological stress, induced by serum depletion, involves growth arrest characterized by an inhibition of DNA synthesis that occurs in the absence of a decrease in histone mRNA or an increase in gadd153 mRNA, one of the growth arrest and DNA damage inducible genes. In contrast, the chemical-induced stress involves growth arrest accompanied by a decrease in histone mRNA, particularly core histone H2B and H2A mRNA, and the induction of gadd153. Chemical-induced changes in histone mRNA inversely correlate to changes in the expression of a stress gene, hsp70, whose expression is dependent upon the maintenance of appropriate nucleosomal structure.
细胞通过激活一系列“急性期”或“应激反应”基因的转录来应对各种应激。这种反应的性质是根据应激的性质量身定制的。生理和病理生理诱导的生长停滞在多大程度上共享共同的基因组反应尚不清楚。因此，我们比较了生理诱导（血清和营养物质耗竭）和化学诱导（2-溴-双-（GSyl）HQ和2-溴-6-（GSyl）HQ）应激对肾小管上皮细胞（LLC-PK1）的影响。血清耗竭诱导的对生理应激的反应涉及生长停滞，其特征是DNA合成受到抑制，这种抑制发生在组蛋白mRNA没有减少或生长停滞和DNA损伤诱导基因之一gadd153 mRNA没有增加的情况下。相反，化学诱导的应激涉及生长停滞，同时伴有组蛋白mRNA减少，特别是核心组蛋白H2B和H2A mRNA减少，以及gadd153的诱导。化学诱导的组蛋白mRNA变化与应激基因hsp70表达的变化呈负相关，hsp70的表达取决于适当核小体结构的维持。
