Das D K, Maulik N, Moraru I I
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110, USA.
J Mol Cell Cardiol. 1995 Jan;27(1):181-93. doi: 10.1016/s0022-2828(08)80017-x.
It is apparent from the above discussion that acute stress, such as ischemia and reperfusion, hypoxia and reoxygenation, hyperthermia and oxidative stress, can rapidly potentiate the induction of genes for certain members of the HSP families and for antioxidants/antioxidant enzymes. Whether the stress response and induction of these genes have a direct role in myocardial protection is not known, but the induction of the expression of these genes are mostly associated with the preservation of myocardial cells from subsequent injury resulting from ischemia, hypoxia and reperfusion. The ubiquitous presence of some of these stress genes, such as for HSP 70 and catalase, in normal unstressed myocardium further suggests a role of these genes in many basic and essential biochemical and metabolic pathways. It is reasonable to speculate that the cells respond to the stress as a consequence of perturbations of one or more of the metabolic pathways by stimulating the induction of the stress genes of that particular pathway in which they participate. Thus, these genes are likely to be involved both in the protection and recovery/repair mechanisms. The precise mechanism by which myocardial cell recognizes and responds to a particular stress agent such as ischemia, hypoxia, hyperthermia or oxidative stress is not clear. While it is tempting to speculate that a generalized mechanism exists, applying to all different modes of stress response and gene induction, whether these agents induce the response via independent pathways or converge within a single point is entirely unclear. However, from the striking resemblance between the pattern of gene expression, especially with regard to HSP and antioxidant genes, it is reasonable to hypothesize the existence of a common and essential pathway of molecular signaling that leads to the expression of these stress genes (Fig. 2). The identification and characterization of the transcription factors that regulate the expression of the genes induced by these forms of stress should greatly facilitate our future understanding of the mechanism of stress response.
从上述讨论中可以明显看出，急性应激，如缺血与再灌注、缺氧与复氧、高热与氧化应激，能够迅速增强热休克蛋白家族某些成员以及抗氧化剂/抗氧化酶相关基因的诱导表达。这些基因的应激反应和诱导表达是否在心肌保护中直接发挥作用尚不清楚，但这些基因表达的诱导大多与保护心肌细胞免受缺血、缺氧和再灌注所致的后续损伤有关。其中一些应激基因，如热休克蛋白70和过氧化氢酶基因，在正常未受应激的心肌中普遍存在，这进一步表明这些基因在许多基本且重要的生化和代谢途径中发挥作用。合理推测，细胞通过刺激其参与的特定代谢途径的应激基因的诱导表达来应对因一种或多种代谢途径紊乱而产生的应激。因此，这些基因可能参与保护以及恢复/修复机制。心肌细胞识别并应对诸如缺血、缺氧、高热或氧化应激等特定应激因素的确切机制尚不清楚。虽然很容易推测存在一种适用于所有不同应激反应和基因诱导模式的通用机制，但这些应激因素是通过独立途径诱导反应还是在某一点汇聚，目前完全不清楚。然而，从基因表达模式，尤其是热休克蛋白和抗氧化基因的表达模式之间的显著相似性来看，合理假设存在一条共同且基本的分子信号通路，该通路导致这些应激基因的表达（图2）。鉴定和表征调节这些应激形式诱导的基因表达的转录因子，应能极大地促进我们未来对应激反应机制的理解。
