Na-K-Cl Cotransporter Molecular Expression & Function During Development

Na-K-Cl 协同转运蛋白分子表达

• 批准号: 6496378
• 负责人: Lynn M Iwamoto
• 金额: $ 17.32万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6496378
• 关键词: chloride ion; clinical research; cooperative study; developmental genetics; erythrocytes; erythroid stem cell; essential hypertension; furosemide; gene expression; gestational age; guinea pigs; human fetus tissue; human subject; immunocytochemistry; ion transport; membrane transport proteins; muscle relaxation; pharmacogenetics; posttranslational modifications; potassium ion; respiratory muscles; sodium ion; tissue /cell culture

The Na-K-2Cl (sodium-potassium-2-chloride) cotransporter is an electroneutral membrane protein that plays several important roles in cellular physiology. Recent data suggest that the Na-K-2CI cotransporter may play a role in airway smooth muscle relaxation. However, molecular identification of this co-transporter protein airway smooth muscle has not been confirmed. More fundamentally, this cotransporter protein in airway smooth muscle has not been confirmed. More fundamentally, this cotransporter regulates salt and water secretion across epithelial cells and maintenance and regulation of cell volume and ion gradients in epithelial and non-epithelial cells (e.g., erythrocytes). The erythrocyte cotransporter appears important because the level of activity in adults with essential hypertension has been correlated with the diuretic and natriuretic responses to furosemide, suggesting genetic variation in cotransporter regulation. Characterization of the Na-K-2Cl cotransporter in human erythroid progenitor cells and neonatal erythrocytes would provide information about developmental changes in the cotransporter expression and function. The present proposal focuses on the Na-K-2CL cotransporter in the neonatal guinea pig and human fetal airways and in the human neonatal erythrocyte and its precursor, the erythroid progenitor cell. The following hypotheses will be tested: 1) the Na-K-2Cl cotransporter is expressed in airway smooth muscle; 2) changes in erythrocyte cotransporter expression and activity occur with maturation; and 3) the regulation of the human Na-K-2Cl cotransporter is similar to that found in animal paradigms. Results of this project will further our understanding of the importance of the Na-K-2Cl cotransporter by providing evidence for its role in loop diuretic mediated airway smooth muscle relaxation. Also, characterization of the Na-K-2Cl cotransporter in the human erythrocyte with the study of its function and changes in maturation may provide new insights into the developmental regulation of this cotransporter as well as in understanding kidney function and the development of essential hypertension.

Na-K-2Cl（钠-钾-2-氯）协同转运蛋白是一种电中性膜蛋白，在细胞生理学中起着几个重要作用。最近的数据表明，Na-K-2CI协同转运蛋白可能在气道平滑肌松弛中发挥作用。然而，这种协同转运蛋白气道平滑肌的分子鉴定尚未得到证实。更重要的是，气道平滑肌中的这种协同转运蛋白尚未得到证实。更根本的是，这种协同转运蛋白调节跨上皮细胞的盐和水分泌以及上皮和非上皮细胞中细胞体积和离子梯度的维持和调节（例如，红细胞）。红细胞协同转运蛋白似乎很重要，因为在成人原发性高血压的活动水平已与利尿剂和利尿钠反应速尿，提示协同转运蛋白调节的遗传变异。人红系祖细胞和新生儿红细胞中Na-K-2Cl协同转运蛋白的表征将提供关于协同转运蛋白表达和功能的发育变化的信息。本提案的重点是在新生豚鼠和人胎儿气道和人新生儿红细胞及其前体，红系祖细胞的Na-K-2CL协同转运。将检验以下假设：1）Na-K-2Cl协同转运蛋白在气道平滑肌中表达; 2）红细胞协同转运蛋白表达和活性随成熟发生变化; 3）人Na-K-2Cl协同转运蛋白的调节与动物模型中发现的相似。该项目的结果将为Na-K-2Cl协同转运蛋白在环路利尿剂介导的气道平滑肌松弛中的作用提供证据，从而进一步加深我们对Na-K-2Cl协同转运蛋白重要性的理解。此外，表征的Na-K-2Cl转运蛋白在人红细胞中的功能和成熟的变化的研究，可能会提供新的见解，这种转运蛋白的发育调节，以及在了解肾功能和原发性高血压的发展。