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 >> 生物化学 分类： 生物学 >> 分子生物学 提交时间： 2024-01-25
摘要： 目的：通过分析小鼠自主食用不同甜味物质后尿液蛋白质组的变化，探索其对机体的可能影响。方法：收集C57BL/6l小鼠主动食用甜味物质前后的尿液样品。甜味物质包括目前世界范围内应用较为广泛且能引起小鼠喜好反应的蔗糖、甜菊糖苷、安赛蜜、三氯蔗糖，其中非营养性甜味剂的浓度选择了已有研究显示的小鼠喜好反应最强烈的浓度。通过高效液相色谱串联质谱联用（LC-MS/MS）的非标记定量蛋白质组学技术进行分析，成组筛选尿液蛋白质组的差异蛋白，进行蛋白质功能和生物学过程分析；进行单只小鼠食用甜味物质前后尿液蛋白质组比较；并将不同甜味物质进行横向对比。结果及结论：尿液蛋白质组可以反映小鼠自主食用甜味物质后的机体变化，且小鼠自主食用的不同甜味物质对尿液蛋白质组的影响并不相同。4种甜味物质中，三氯蔗糖与蔗糖引起机体的变化最为相似，甜菊糖苷与蔗糖引起机体的变化相差最远；蔗糖、安赛蜜和三氯蔗糖引起的机体变化相似，而甜菊糖苷引起机体的变化与其他甜味物质不同。小鼠自主食用4种甜味物质后尿液蛋白质组差异蛋白中均有已经被报道的与脑奖励回路相关的蛋白，而只有自主食用蔗糖、安赛蜜和三氯蔗糖后尿液蛋白质组差异蛋白大量与代谢过程相关，自主食用甜菊糖苷后尿液蛋白质组差异蛋白主要与核小体组装、基因表达等过程相关。
分类： 生物学 >> 生物化学 分类： 生物学 >> 分子生物学 提交时间： 2024-01-02
摘要： 目的：对肥胖人群与正常人群尿液蛋白质组的比较。方法：收集肥胖人群和正常人群的尿液样品，通过高效液相色谱串联质谱联用（LC-MS/MS）的非标记定量蛋白质组学技术进行鉴定。筛选肥胖人群与正常人群尿液蛋白质组的差异蛋白进行蛋白质功能和生物学通路分析；将肥胖个人与正常人群尿液蛋白质组进行比较，统计共有差异蛋白进行蛋白质功能和生物学通路分析；在肥胖个人尿液蛋白质组中检索已被报道的肥胖生物标志物。结果：肥胖人群相对于正常人群尿液蛋白质组可鉴定到38个差异蛋白，其中有些蛋白已经被报道与代谢、肥胖相关，差异蛋白富集到的生物学过程也与代谢等过程相关；肥胖个人与正常人群尿液蛋白质组比较富集到８个共有差异蛋白，其中有蛋白已经被报道与代谢、肥胖相关，差异蛋白富集到的生物学过程也与代谢等过程相关；在肥胖个人相对于正常人群尿液蛋白质组的差异蛋白中，能匹配到已被报道的肥胖生物标志物。结论：尿液蛋白质组能进行正常人与肥胖者的区分，尿液蛋白质组差异蛋白中具有已知和肥胖、代谢相关的关键蛋白，且差异蛋白能富集到营养、代谢等相关生物学过程。尿液蛋白质组具有探究肥胖发生机制、提供个性化治疗的潜力。
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