Salicylic Acid in Immunity and Health: A Small Phytohormone with Big Physiological Impacts

免疫系统的本质是确保对病原体的防御，而不会对 赛尔夫。在植物中，这部分是通过调节免疫信号水杨酸(SA)来实现的。 效应触发免疫(ETI)过程中SA的产生与细胞程序性死亡有关 (PCD)，以限制病原体在感染部位的生长和远端细胞的存活 广谱系统获得性抗性(SAR)。SA的这种二元功能通过以下方式实现 NPR1的活动。NPR1不仅是一种主要的免疫调节因子，而且还参与关键的细胞功能， 比如生物钟。在没有病原体挑战的情况下，SA是通过 直接调节时钟成分ChE，随后控制NPR1的核转位。 NPR1不仅是SA介导的防御基因表达所必需的，而且早晨和 晚间时钟基因。因此，npr1突变体对感染是超敏的，并具有显著的 抑制了时钟的活动。然而，PCD是如何在感染部位执行的，NPR1如何抑制PCD 在远端细胞中并促进SAR，以及生物钟在调节SAR中起什么作用。 存在的根本性问题。这个项目将研究核孔复杂的渗透性是如何 在感染细胞中执行ETI/PCD时，核内钙离子特异性增加，并检测 假设NPR1重新编程防御转录组并促进远端细胞作为一种 通过SA诱导的NPR1形成CUL3泛素连接酶复合体的底物适配器 在胞核和胞浆内凝聚。该项目还将通过以下方式确定该机制 哪种胆碱酯酶在全身组织中被激活以诱导SA合成并解释为什么时钟成分 参与监管特区的这一关键步骤。最后，将进行遗传分析，以提供 时钟调节SA免疫反应朝向清晨门控的分子基础 植物在夜间干燥，并强调在一天的时间内使用化学物质的重要性 用于农业和医药，以最大限度地提高疗效和减少副作用。这一不断发展的 该项目符合NIGMS的使命，即“了解作为基础的原则、机制和过程 生物有机体，通常使用研究模型“和米拉资助模型。除了显而易见的 对基础生物学和农业的重要意义，该项目可能会有更广泛的影响，因为SA是 人类已知的最古老的草药。近年来，阿司匹林(乙酰化SA)已被重新调整用途 用于治疗心血管疾病和某些类型的癌症(如结肠癌)。非乙酰化SA 在临床试验中，衍生物在治疗II型糖尿病方面显示出了良好的效果。然而， 这些不同药效的潜在机制尚不完全清楚，问题是 在如何提高药物疗效的同时减少副作用(例如出血)的问题必须得到解决。

The essence of an immune system is to ensure defense against pathogens without collateral damage to self. In plants, this is accomplished, in part, through the regulation of the immune signal salicylic acid (SA). Production of SA during the effector-triggered immunity (ETI) is associated with programmed cell death (PCD) of the infected cells to restrict pathogen growth at the site of infection and survival of distal cells with broad-spectrum systemic acquired resistance (SAR). This binary function of SA is achieved through activities of NPR1. NPR1 is not only a master immune regulator, but also involved in key cellular functions, such as the circadian clock. In the absence of pathogen challenge, SA is rhythmically produced through the direct regulation of the clock component CHE and subsequently controls the nuclear translocation of NPR1. NPR1 is required for the expression of not only SA-mediated defense genes, but also both morning and evening clock genes. Hence, the npr1 mutant is hypersusceptible to infection and has significantly dampened clock activities. However, how PCD is executed at the site of infection, how NPR1 inhibits PCD in distal cells and promotes SAR, and what role the circadian clock plays in regulating SAR are long- standing fundamental questions. This project will investigate how the nuclear pore complex permeability and the nuclear Ca2+ are specifically increased in executing ETI/PCD in infected cells and test the hypothesis that NPR1 reprograms the defense transcriptome and promotes survival of distal cells as a substrate adaptor for the Cul3 ubiquitin ligase complex through the formation of SA-induced NPR1 condensates in both the nucleus and the cytoplasm. The project will also determine the mechanism by which CHE is activated in systemic tissue to induce SA synthesis and explain why a clock component is involved in regulating this key step of SAR. Finally, genetic analysis will be performed to provide the molecular basis for the clock-mediated gating of the SA immune response towards the morning in avoiding plant desiccation at night and to highlight the importance of time-of-the-day chemical application in agriculture and in medicine for maximizing efficacy and reducing side effects. This continuously developing project fits the NIGMS mission of “understanding the principles, mechanisms, and processes that underlie living organisms, often using research models” and the MIRA funding model. Besides its obvious significance to basic biology and agriculture, the project may have even broader implications because SA is the oldest herbal medicine known to mankind. In recent years, aspirin (acetylated SA) has been repurposed in treating cardiovascular diseases and certain types of cancer (e.g., colon cancer). Non-acetylated SA derivatives have shown promising results in treating type II diabetes in clinical trials. However, the underlying mechanisms for these diverse medicinal effects are not completely understood and the issue over how to enhance the drug efficacy while reducing the side effect (e.g., bleeding) has to be addressed.