Institute of Biochemistry, Carleton University, Ottawa, Ont., Canada.
Int J Biol Sci. 2010 Jan 7;6(1):9-50. doi: 10.7150/ijbs.6.9.
Studies of the molecular mechanisms that are involved in stress responses (environmental or physiological) have long been used to make links to disease states in humans. The nematode model organism, Caenorhabditis elegans, undergoes a state of hypometabolism called the 'dauer' stage. This period of developmental arrest is characterized by a significant reduction in metabolic rate, triggered by ambient temperature increase and restricted oxygen/ nutrients. C. elegans employs a number of signal transduction cascades in order to adapt to these unfavourable conditions and survive for long times with severely reduced energy production. The suppression of cellular metabolism, providing energetic homeostasis, is critical to the survival of nematodes through the dauer period. This transition displays molecular mechanisms that are fundamental to control of hypometabolism across the animal kingdom. In general, mammalian systems are highly inelastic to environmental stresses (such as extreme temperatures and low oxygen), however, there is a great deal of conservation between the signal transduction pathways of nematodes and mammals. Along with conserving many of the protein targets in the stress response, many of the critical regulatory mechanisms are maintained, and often differ only in their level of expression. Hence, the C. elegans model outlines a framework of critical molecular mechanisms that may be employed in the future as therapeutic targets for addressing disease states.
长期以来,对涉及应激反应(环境或生理)的分子机制的研究一直被用来将其与人类疾病状态联系起来。秀丽隐杆线虫作为一种线虫模式生物,会经历一种称为“ dauer”阶段的低代谢状态。这种发育停滞期的特征是代谢率显著降低,这是由环境温度升高和氧气/营养物质限制引发的。为了适应这些不利条件,秀丽隐杆线虫会利用许多信号转导级联反应来生存,并在严重减少能量产生的情况下长时间存活。抑制细胞代谢,提供能量平衡,对于线虫通过 dauer 期的生存至关重要。这种转变展示了控制动物界低代谢的基本分子机制。一般来说,哺乳动物系统对环境压力(如极端温度和低氧)的弹性很差,然而,线虫和哺乳动物的信号转导途径之间有很大的保守性。除了在应激反应中保留许多蛋白质靶标外,许多关键的调节机制也得以维持,而且通常只是在表达水平上有所不同。因此,秀丽隐杆线虫模型概述了一个可能在未来作为治疗疾病状态的治疗靶点的关键分子机制框架。