Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, 117997, Moscow, Russia.
Moscow Institute of Physics and Technology, 141701, Dolgoprudnyi, Moscov oblast, Russia.
Dokl Biol Sci. 2022 Aug;505(1):113-118. doi: 10.1134/S0012496622040056. Epub 2022 Aug 29.
The most important property of a living organism is the maintenance of optimal acid-base balance and the ionic composition of the internal environment. The kidneys are one of the main pH-regulating organs in the body. Receptor tyrosine kinase IRR (an insulin receptor-related receptor) is an alkaline pH-sensor. In mice (Mus Musculus) with a knockout of the insrr gene encoding the IRR receptor, bicarbonate secretion is impaired under the conditions of alkaline loading, which indicates the role of the receptor tyrosine kinase IRR in the regulation of acid-base balance in the body. In order to search for proteins functionally associated with the receptor tyrosine kinase IRR, we performed a large-scale sequencing of the mouse kidney transcriptome of wild type and insrr knockout mice kept under normal conditions and under alkaline conditions. As a result, we found a decrease in the gapdh gene expression in the kidneys of insrr knockout mice compared to wild type mice. RNA sequencing data were confirmed by TaqMan real-time PCR and Western blotting. Using the TaqMan real-time PCR method, we revealed a decrease in the level of gapdh expression not only in the kidneys, but also in the liver and brain of insrr knockout mice. Thus, the changes in the gapdh gene expression in the kidneys of insrr knockout mice may indicate a functional relationship between genes and a possible role of GAPDH in previously undescribed molecular mechanisms of regulation of acid-base balance in the body.
生物体最重要的特性是维持最佳酸碱平衡和内环境离子组成。肾脏是体内主要的 pH 调节器官之一。受体酪氨酸激酶 IRR(胰岛素受体相关受体)是一种碱性 pH 传感器。在缺失编码 IRR 受体的 insrr 基因的小鼠(Mus Musculus)中,在碱性负荷条件下碳酸氢盐分泌受损,这表明受体酪氨酸激酶 IRR 在调节体内酸碱平衡中起作用。为了寻找与受体酪氨酸激酶 IRR 功能相关的蛋白质,我们对在正常条件和碱性条件下饲养的野生型和 insrr 基因敲除小鼠的肾脏进行了大规模转录组测序。结果发现,与野生型小鼠相比,insrr 基因敲除小鼠肾脏中的 gapdh 基因表达降低。RNA 测序数据通过 TaqMan 实时 PCR 和 Western blot 得到验证。使用 TaqMan 实时 PCR 方法,我们不仅在肾脏,而且在 insrr 基因敲除小鼠的肝脏和大脑中发现 gapdh 表达水平降低。因此,insrr 基因敲除小鼠肾脏中 gapdh 基因表达的变化可能表明基因之间存在功能关系,以及 GAPDH 可能在以前未描述的体内酸碱平衡调节的分子机制中发挥作用。