Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Cell Mol Life Sci. 2021 Dec 16;79(1):41. doi: 10.1007/s00018-021-04043-x.
Living organisms repeatedly encounter stressful events and apply various strategies to survive. Polyamines are omnipresent bioactive molecules with multiple functions. Their transient synthesis, inducible by numerous stressful stimuli, is termed the polyamine stress response. Animals developed evolutionarily conserved strategies to cope with stresses. The urea cycle is an ancient attribute that deals with ammonia excess in terrestrial species. Remarkably, most fish retain the urea cycle genes fully expressed during the early stages of development and silenced in adult animals. Environmental challenges instigate urea synthesis in fish despite substantial energetic costs, which poses the question of the urea cycle's evolutionary significance. Arginase plays a critical role in oxidative stress-dependent reactions being the final urea cycle enzyme. Its unique subcellular localization, high inducibility, and several regulation levels provide a supreme ability to control the polyamine synthesis rate. Notably, oxidative stress instigates the arginase-1 activity in mammals. Arginase is also dysregulated in aging organisms' brain and muscle tissues, indicating its role in the pathogenesis of age-associated diseases. We designed a study to investigate the levels of the urea cycle and polyamine synthesis-related enzymes in a fish model of acute hypoxia. We evidence synchronized elevation of arginase-2 and ornithine decarboxylase following oxidative stress in adult fish and aging animals signifying the specific function of arginase-2 in fish. Moreover, we demonstrate oxidative stress-associated polyamine synthesis' induction and urea cycle' arrest in adult fish. The subcellular arginase localization found in the fish seems to correspond to its possible evolutionary roles.
生物体反复遇到应激事件，并应用各种策略来生存。多胺是普遍存在的具有多种功能的生物活性分子。它们的短暂合成，可被许多应激刺激诱导，被称为多胺应激反应。动物进化出了保守的策略来应对压力。尿素循环是一种古老的属性，用于处理陆地物种中的氨过量。值得注意的是，大多数鱼类在发育的早期阶段保留了完全表达的尿素循环基因，而在成年动物中则沉默。尽管存在大量的能量成本，环境挑战会促使鱼类合成尿素，但这引发了关于尿素循环进化意义的问题。精氨酸酶在依赖氧化应激的反应中发挥关键作用，是尿素循环的最后一种酶。其独特的亚细胞定位、高诱导性和几个调节水平提供了控制多胺合成速率的卓越能力。值得注意的是，氧化应激会引发哺乳动物的精氨酸酶-1活性。精氨酸酶在衰老生物体的大脑和肌肉组织中也失调，表明其在与年龄相关疾病的发病机制中的作用。我们设计了一项研究，以调查急性缺氧鱼类模型中尿素循环和多胺合成相关酶的水平。我们的证据表明，成年鱼类和衰老动物在氧化应激后，精氨酸酶-2 和鸟氨酸脱羧酶的水平同步升高，这表明精氨酸酶-2在鱼类中的特定功能。此外，我们还证明了成年鱼类中与氧化应激相关的多胺合成诱导和尿素循环停滞。在鱼类中发现的亚细胞精氨酸酶定位似乎与其可能的进化角色相对应。
