分类： 生物学 >> 分子生物学 提交时间： 2024-05-24
摘要： Differential and even opposing functions of two major antioxidant transcription factors Nrf1 and Nrf2 (encoded by Nfe2l1 and Nfe2l2, respectively) are determined by distinctions in their tempospatial positioning, topological repartitioning, proteolytic processing, and biochemical modification, as well as in their shared evolutionary origin. As a matter of fact, the allelopathic potentials of Nrf1 and Nrf2 (both resembling two entangled ‘Yin-Yang’ quanta that comply with a dialectic law of the unity of opposites) are fulfilled to coordinately control redox physiological homeostasis so as to be maintained within the presetting thresholds. By putative exponential curves of redox stress and intrinsic anti-redox capability, there is inferable to exist a set point at approaching zero with the ‘Golden Mean’ for the healthy survival (i.e., dubbed the ‘zero theory’). A bulk of the hitherto accumulating evidence demonstrates that the set point of redox homeostasis is dictated selectively by multi-hierarchical threshold settings, in which the living fossil-like Nrf1 acts as a robust indispensable determinon, whereas Nrf2 serves as a versatile chameleon-like master regulon, in governing the redox homeodynamic ranges. This is attributable to the facts that Nrf2 has exerted certain ‘double-edged sword’ effects on life process, whereas Nrf1 executes its essential physiobiological functions, along with unique pathophysiological phenotypes, by integrating its ‘three-in-one’ roles elicited as a specific triplet of direct sensor, transducer and effector within multi-hierarchical stress responsive signaling to redox metabolism and target gene reprogramming. Here, we also critically reviewed redox regulation of physio-pathological functions from the eco-evo-devo perspectives, through those coding rules (redox code, stress-coping code, and topogenetic code). The evolving concepts on stress and redox stress were also further revisited by scientific principles of physics and chemistry, apart from two novel concepts of ‘oncoprotists’ and ‘reverse central dogma’ being introduced in this interdisciplinary and synthetic review.
分类： 生物学 >> 动物学 提交时间： 2018-12-25 合作期刊: 《动物营养学报》
摘要： Klotho是一种最近发现的抗衰老基因，它的缺失或突变会导致小鼠在出生3~4周后表现出衰老现象，相反，其过表达可增强小鼠的抗氧化能力，并延长小鼠寿命。目前研究表明，Klotho蛋白发挥抗氧化应激功能可能是通过激活叉头状转录因子O（FoxO）的转录活性、激活环磷酸腺苷（cAMP）信号通路、激活Kelch样环氧氯丙烷相关蛋白-1（Keap1）-核因子E2相关因子2（Nrf2）/抗氧化反应元件（ARE）信号通路来实现的。本文就Klotho的发现、结构特征、表达及其蛋白与氧化应激之间的关系进行综述，以期为畜牧生产中缓解动物氧化应激提供思路。
分类： 生物学 >> 动物学 提交时间： 2017-10-23 合作期刊: 《动物营养学报》
摘要： Kelch样环氧氯丙烷相关蛋白–核因子E2相关因子2–抗氧化反应元件（Keap1-Nrf2-ARE）信号通路是机体细胞抵制氧化应激损伤和异生物质损伤最为重要的一种防御机制，且该通路与炎性疾病包括癌症、神经变性疾病、心血管疾病、衰老等密切相关。Nrf2信号的激活可诱导与ARE相关基因的各种解毒酶、抗氧化防御酶和抗氧化蛋白酶的表达的转录调控，且调控Keap1-Nrf2-ARE信号通路已成为预防和治疗氧化应激相关疾病和炎性疾病的一个强有力的靶目标。该文重点综述了氧化应激、Keap1-Nrf2-ARE信号通路在抗氧化应激中的作用及相关的调控剂。
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