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: 6262820
• 负责人: Lynn M Iwamoto
• 金额: $ 39万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6262820
• 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（2-氯化钠钾）协同转运蛋白是一种电中性膜蛋白，在细胞生理学中发挥着多种重要作用。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。更根本的是，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上皮细胞上盐和水的分泌，以及上皮细胞和非上皮细胞（例如红细胞）中细胞体积和离子梯度的维持和调节。红细胞协同转运蛋白显得很重要，因为患有原发性高血压的成人的活性水平与速尿的利尿和钠尿反应相关，这表明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有关协同转运蛋白表达和功能的发育变化的信息。本提案重点关注新生豚鼠和人类胎儿气道以及人类新生儿红细胞及其前体红系祖细胞中的 Na-K-2CL 协同转运蛋白。将测试以下假设：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着成熟而发生变化； 3) 人类 Na-K-2Cl 协同转运蛋白的调节与动物范例中发现的相似。该项目的结果将通过提供证据证明 Na-K-2Cl 协同转运蛋白在袢利尿剂介导的气道平滑肌松弛中的作用，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，人红细胞中 Na-K-2Cl 协同转运蛋白的表征及其功能和成熟变化的研究可能为该协同转运蛋白的发育调节以及了解肾功能和原发性高血压的发展提供新的见解。