Departments of Molecular Cell Physiology and Bio-Ionomics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Japan Institute for Food Education and Health, St. Agnes' University, Kyoto, Japan.
Ann N Y Acad Sci. 2017 Jun;1398(1):142-151. doi: 10.1111/nyas.13361. Epub 2017 Jun 2.
Flavonoids keep us healthy by controlling various body and cellular functions. It is well known that cations, such as Na , K , and Ca , play important roles in the regulation of body and cellular functions, including generation of action potentials and the resting membrane potential of neural and muscle cells and signal transduction as intracellular second messengers. However, we have little information on the physiological roles of anions, particularly Cl , in body and cellular functions. Quercetin, a flavonoid, stimulates Na -K -2Cl cotransporter 1 (NKCC1), which is one of the most important ion transporters regulating the cytosolic Cl concentration ([Cl ] ). Here, we introduce the molecular mechanism by which flavonoids, specifically quercetin, act through elevation of [Cl ] via activation of NKCC1 on important factors controlling various body and cellular functions, such as (1) antihypertensive actions controlling blood volume dependent on the amounts of renal Na reabsorption via expression of the epithelial Na channel, (2) neurite-elongating actions via polymerization of tubulin by inhibiting GTPase activity, and (3) antibacterial and antiviral infective actions through stimulation of epithelial Cl secretion by increasing the driving force for epithelial Cl secretion.
类黄酮通过控制各种身体和细胞功能来保持我们的健康。众所周知，阳离子，如 Na+、K+和 Ca2+，在调节身体和细胞功能方面发挥着重要作用，包括产生动作电位和神经和肌肉细胞的静息膜电位以及作为细胞内第二信使的信号转导。然而，我们对阴离子，特别是 Cl-在身体和细胞功能中的生理作用知之甚少。类黄酮槲皮素刺激 Na+-K+-2Cl-共转运蛋白 1（NKCC1），它是调节细胞溶质 Cl-浓度 ([Cl-]) 的最重要的离子转运蛋白之一。在这里，我们介绍了类黄酮，特别是槲皮素，通过通过激活 NKCC1 升高 [Cl-] 从而发挥作用的分子机制，这对控制各种身体和细胞功能的重要因素有影响，例如：（1）通过上皮 Na 通道的表达控制与肾 Na 重吸收量相关的血容量的降压作用，（2）通过抑制 GTP 酶活性使微管蛋白聚合的神经突延伸作用，和（3）通过增加上皮 Cl 分泌的驱动力刺激上皮 Cl 分泌的抗菌和抗病毒感染作用。
