Salicylic acid in immunity and health: A small phytohormone with big physiological impacts

 描述（由申请人提供）：水杨酸（SA）是人类已知的最古老的草药。近年来，长期使用"婴儿"阿司匹林（乙酰化SA）已被证明可以预防心血管疾病，并显着减少某些类型的癌症（例如，结肠癌）。非乙酰化SA衍生物在临床试验中显示出治疗II型糖尿病的有希望的结果。然而，这种小酚类化合物如何具有如此多样的药用效果尚不完全清楚。SA是在病原体攻击时诱导的天然植物免疫信号。SA的局部增加与感染细胞的程序性细胞死亡（PCD）和效应子触发的免疫（ETI）相关。随后，SA合成通过未知机制在全身（未感染）组织中诱导，以促进细胞存活并赋予广谱全身获得性抗性（SAR）。研究表明，SA结合并抑制几种ROS清除酶，并通过细胞氧化还原的变化控制主要免疫调节因子NPR 1的核转位。在细胞核中，NPR 1作为参与PCD/ETI或SAR相关基因表达的多个转录因子的转录辅因子。最近在拟南芥中的研究表明，在没有病原菌的挑战，基础SA水平振荡的昼夜节律的方式，并控制氧化还原敏感的昼夜节律钟组件，CHE。这个时钟组件也需要病原体诱导的SA合成在全身组织在SAR期间，这表明参与的氧化还原和生物钟在传递免疫信号。此外，已经发现NPR 1不仅调节免疫相关基因的转录，而且还调节中枢昼夜节律钟的早晨（LHY，PRR7）以及晚上（TOC1）组分的转录，这表明该免疫调节剂也是生物钟的内在调节剂。该项目将解决的主要问题是生物钟和代谢节律如何整合线索，如SA，以有利于整个生物体的方式计时和同步能量密集型生理过程，如生长和防御。该项目将培养下一代科学家，并做出可能导致更好地理解SA在分子和系统水平上对植物和人类的深远影响的发现。

 DESCRIPTION (provided by applicant): Salicylic acid (SA) is the oldest herbal medicine known to mankind. In recent years, long-term use of "baby" aspirin (acetylated SA) has been shown to prevent cardiovascular diseases and significantly reduce deaths from 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, how this small phenolic compound can have such diverse medicinal effects is not completely understood. SA is naturally a plant immune signal induced upon pathogen challenge. Local increase in SA is associated with programmed cell death (PCD) of infected cells and effector- triggered immunity (ETI). Subsequently, SA synthesis is induced in systemic (non-infected) tissue through an unknown mechanism to promote cell survival and confer broad-spectrum systemic acquired resistance (SAR). Studies showed that SA binds and inhibit several ROS scavenging enzymes and controls the nuclear translocation of the master immune regulator NPR1 through changes in cellular redox. In the nucleus, NPR1 serves as a transcription cofactor for multiple transcription factors involved in PCD/ETI- or SAR-related gene expression. Recent studies in Arabidopsis showed that in the absence of pathogen challenge, the basal SA level oscillates in a circadian manner and is controlled by the redox sensitive circadian clock component, CHE. This clock component is also required for pathogen-induced SA synthesis in systemic tissue during SAR, suggesting the involvement of redox and the circadian clock in transmitting the immune signal. Moreover, NPR1 has been found to regulate transcription of not only immune-related genes, but also the morning (LHY, PRR7) as well as the evening (TOC1) components of the central circadian clock indicating that this immune regulator is also an intrinsic regulator of the clock. The main question that will be addressed by this project is how the circadian clock and the metabolic rhythms integrate cues, such as SA, to time and synchronize energy-intensive physiological processes such as growth and defense in a manner that is beneficial to the whole organism. This project will train the next generation of scientists and make discoveries that may lead to better understanding of the profound effects that SA has in plants and in humans at the molecular and systems level.