Physiological and molecular evidence of heat acclimation memory: a lesson from thermal responses and ischemic cross-tolerance in the heart
Physiological and molecular evidence of heat acclimation memory: a lesson from thermal responses and ischemic cross-tolerance in the heart
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DOI：
10.1152/physiolgenomics.00215.2007
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发表时间：
2008-06-12
影响因子：
4.6
通讯作者：
Horowitz, Michal
中科院分区：
文献类型：
--
作者：
Tetievsky, Anna;Cohen, Omer;Horowitz, Michal
在人类中的零星发现表明，热习服(AC)丧失后重新诱导的速度明显快于最初的AC阶段。动物研究证实，潜在的适应过程是分子的。在这里，我们测试了AC(Reac)的快速再诱导与“分子记忆”有关的假设。在体测量热应激期间的结肠温度分布，以及对心脏对缺血再灌注或缺氧损伤的交叉耐受性的体外评估表明，Reac只需要2天，而AC的初始发展需要30天。试验组的应激基因图谱突出显示转录激活基因簇(37%)，其中包括热休克蛋白(HSP)基因、抗凋亡基因和染色质重塑基因。尽管生理表型已恢复到驯化前状态，但经过1个月的脱驯化(DEAC)后，基因转录本并没有恢复到驯化前的水平，这表明在这个系统中，基因型和表型之间存在着二分法。对HSP70和HSF1转录本的单独检测与这些发现一致。HSP72、HSF1/P-HSF1和Bclxl蛋白图谱遵循观察到的二分基因组反应。相反，作为一种重要的细胞保护成分，HSP90与DEAC上的转录激活不匹配。类似反应的基因簇在de-/reac上的一致激活意味着反应表型可塑性与上游分母有关。在AC、DEAC和REAC期间，HSF1蛋白/磷酸化水平的升高和转录活性染色质重塑基因的维持意味着染色质重塑在转录组和快速细胞保护性适应性记忆的预适应中发挥关键作用。
Sporadic findings in humans suggest that reinduction of heat acclimation (AC) after its loss occurs markedly faster than that during the initial AC session. Animal studies substantiated that the underlying acclimatory processes are molecular. Here we test the hypothesis that faster reinduction of AC (ReAC) implicates "molecular memory." In vivo measurements of colonic temperature profiles during heat stress and ex vivo assessment of cross-tolerance to ischemia-reperfusion or anoxia insults in the heart demonstrated that ReAC only needs 2 days vs. the 30 days required for the initial development of AC. Stress gene profiling in the experimental groups highlighted clusters of transcriptionally activated genes (37%), which included heat shock protein (HSP) genes, antiapoptotic genes, and chromatin remodeling genes. Despite a return of the physiological phenotype to its preacclimation state, after a 1 mo deacclimation (DeAC) period, the gene transcripts did not resume their preacclimation levels, suggesting a dichotomy between genotype and phenotype in this system. Individual detection of hsp70 and hsf1 transcripts agreed with these findings. HSP72, HSF1/P-HSF1, and Bcl-xL protein profiles followed the observed dichotomized genomic response. In contrast, HSP90, an essential cytoprotective component mismatched transcriptional activation upon DeAC. The uniform activation of the similarly responding gene clusters upon De-/ReAC implies that reacclimatory phenotypic plasticity is associated with upstream denominators. During AC, DeAC, and ReAC, the maintenance of elevated/phosphorylated HSF1 protein levels and transcriptionally active chromatin remodeling genes implies that chromatin remodeling plays a pivotal role in the transcriptome profile and in preconditioning to rapid cytoprotective acclimatory memory.