Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion 71110, Crete, Greece.
Nature. 2012 Oct 11;490(7419):213-8. doi: 10.1038/nature11417. Epub 2012 Sep 12.
Heat stroke is a life-threatening condition, characterized by catastrophic collapse of thermoregulation and extreme hyperthermia. In recent years, intensification of heat waves has caused a surge of heat-stroke fatalities. The mechanisms underlying heat-related pathology are poorly understood. Here we show that heat stroke triggers pervasive necrotic cell death and neurodegeneration in Caenorhabditis elegans. Preconditioning of animals at a mildly elevated temperature strongly protects from heat-induced necrosis. The heat-shock transcription factor HSF-1 and the small heat-shock protein HSP-16.1 mediate cytoprotection by preconditioning. HSP-16.1 localizes to the Golgi, where it functions with the Ca(2+)- and Mn(2+)-transporting ATPase PMR-1 to maintain Ca(2+) homeostasis under heat stroke. Preconditioning also suppresses cell death inflicted by diverse insults, and protects mammalian neurons from heat cytotoxicity. These findings reveal an evolutionarily conserved mechanism that defends against diverse necrotic stimuli, and may be relevant to heat stroke and other pathological conditions involving necrosis in humans.
热射病是一种危及生命的病症，其特征是体温调节灾难性崩溃和极度体温过高。近年来，热浪的加剧导致热射病死亡人数激增。与热相关的病理机制还了解甚少。在这里，我们表明热射病会在秀丽隐杆线虫中引发广泛的坏死性细胞死亡和神经退行性变。在稍高的温度下对动物进行预处理强烈地保护其免受热诱导的坏死。热休克转录因子 HSF-1 和小分子热休克蛋白 HSP-16.1 通过预处理介导细胞保护。HSP-16.1 定位于高尔基体，在那里它与 Ca(2+)和 Mn(2+)转运 ATP 酶 PMR-1 一起作用，以维持热休克下的 Ca(2+)稳态。预处理还抑制了多种损伤引起的细胞死亡，并保护哺乳动物神经元免受热细胞毒性。这些发现揭示了一种保守的机制，该机制可以抵抗多种坏死性刺激，可能与热射病和其他涉及人类坏死的病理状况有关。
