Dinh H K, Stavchansky S, Schuschereba S T, Stuck B E, Bowman P D
Division of Pharmaceutics, The University of Texas at Austin, Austin, TX, USA.
Pharmacogenomics J. 2002;2(5):318-26. doi: 10.1038/sj.tpj.6500120.
Herbimycin A (HA), a known inducer of the heat shock response, was investigated for its ability to increase survival of a human cell line following thermal injury. Its effect on transcriptional activity was also assessed with cDNA arrays to provide new targets for cytoprotection. Pretreatment with at least 0.75 microg/ml HA significantly increased the fraction of cells surviving thermal injury by up to 50% (based on 8s exposure) compared to untreated controls. HA also significantly induced transcription of mRNA for HSP90 and HSP70, and protein production for HSP40 and HSP70. Gene expression profiling demonstrated that the most highly elevated genes included growth factors and transcription factors, while prominently suppressed genes included transcription factors and kinases. These results suggest that cytoprotection may be due to the contribution of the products of a significant number of genes in addition to the classic stress response genes, suggesting that modulation of these genes might induce thermotolerance and amelioration of thermal injury.
赫比霉素A（HA）是一种已知的热休克反应诱导剂，本研究考察了其在热损伤后提高人细胞系存活率的能力。还利用cDNA阵列评估了其对转录活性的影响，以提供细胞保护的新靶点。与未处理的对照相比，用至少0.75微克/毫升的HA预处理可使热损伤后存活的细胞比例显著增加高达50%（基于8秒暴露）。HA还显著诱导HSP90和HSP70的mRNA转录以及HSP40和HSP70的蛋白质生成。基因表达谱分析表明，上调最显著的基因包括生长因子和转录因子，而显著下调的基因包括转录因子和激酶。这些结果表明，细胞保护可能不仅归因于经典应激反应基因的产物，还归因于大量基因的贡献，这表明对这些基因的调控可能诱导热耐受性并改善热损伤。
