Nutritional Immunology and Molecular Nutrition Group, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Curr Med Chem. 2010;17(5):467-78. doi: 10.2174/092986710790226110.
Since its discovery in the early 1960's, abscisic acid (ABA) has received considerable attention as an important phytohormone, and more recently, as a candidate medicinal in humans. In plants it has been shown to regulate important physiological processes such as response to drought stress, and dormancy. The discovery of ABA synthesis in animal cells has generated interest in the possible parallels between its role in plant and animal systems. The importance of this molecule has prompted the development of several methods for the chemical synthesis of ABA, which differ significantly from the biosynthesis of ABA in plants through the mevalonic acid pathway. ABA recognition in plants has been shown to occur at both the intra- and extracellularly but little is known about the perception of ABA by animal cells. A few ABA molecular targets have been identified in vitro (e.g., calcium signaling, G protein-coupled receptors) in both plant and animal systems. A unique finding in mammalian systems, however, is that the peroxisome proliferator-activated receptor, PPAR gamma, is upregulated by ABA in both in vitro and in vivo studies. Comparison of the human PPAR gamma gene network with Arabidopsis ABA-related genes reveal important orthologs between these groups. Also, ABA can ameliorate the symptoms of type II diabetes, targeting PPAR gamma in a similar manner as the thiazolidinediones class of anti-diabetic drugs. The use of ABA in the treatment of type II diabetes, offers encouragement for further studies concerning the biomedical applications of ABA.
自 20 世纪 60 年代初发现以来,脱落酸(ABA)作为一种重要的植物激素受到了相当多的关注,最近,它也被认为是人类的候选药物。在植物中,它被证明可以调节重要的生理过程,如对干旱胁迫的反应和休眠。动物细胞中 ABA 合成的发现引起了人们对其在植物和动物系统中的作用可能存在相似性的兴趣。这种分子的重要性促使人们开发了几种 ABA 的化学合成方法,这些方法与植物中通过甲羟戊酸途径合成 ABA 有很大的不同。已经证明 ABA 在植物体内和细胞外都能被识别,但对于动物细胞对 ABA 的感知知之甚少。已经在植物和动物系统中鉴定出了一些 ABA 的分子靶点(例如,钙信号、G 蛋白偶联受体)。然而,在哺乳动物系统中一个独特的发现是,过氧化物酶体增殖物激活受体(PPARγ)在体外和体内研究中都被 ABA 上调。将人类 PPARγ基因网络与拟南芥 ABA 相关基因进行比较,揭示了这些基因之间的重要同源物。此外,ABA 可以改善 II 型糖尿病的症状,以类似于噻唑烷二酮类抗糖尿病药物的方式靶向 PPARγ。ABA 在治疗 II 型糖尿病中的应用,为进一步研究 ABA 在生物医学中的应用提供了鼓励。