CHOLINE TRANSPORTERS SPECIFICALLY TARGET NON-NEURONAL ACETYLCHOLINE SYNTHESIS

胆碱转运蛋白专门针对非神经元乙酰胆碱合成

• 批准号: 7958505
• 负责人: Pill-Soon Song
• 金额: $ 6.04万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958505
• 关键词: Acetylcholine; Asthma; Cell Proliferation; Cells; Choline; Computer Retrieval of Information on Scientific Projects Database; Coupled; Data; Epithelial Cells; Funding; Grant; Institution; Link; Lung; Lung diseases; Malignant Epithelial Cell; Malignant neoplasm of lung; Mediating; Modeling; Neuroendocrine Cell; Neuroglia; Neurons; Play; Primates; Proteins; Research; Research Personnel; Resources; Role; Signal Transduction; Sodium; Source; Squamous Cell Lung Carcinoma; Testing; United States National Institutes of Health; choline transporter; cholinergic; knock-down; lung Carcinoma; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Non-neuronal acetylcholine (Ach) synthesis and secretion may play a role in lung diseases such as lung cancer and asthma. In order to characterize and target non-neuronal signaling in the lung it is necessary to identify a step that differs between neuronal and non-neuronal cholinergic signaling. Choline uptake is a rate-limiting step for ACh synthesis and may provide this target. In neurons, the sodium-dependent, high-affinity choline transporter (CHT1) is absolutely required to transport choline into neurons for ACh synthesis. Our preliminary data shows that CHT1 is not required by some lung cells for ACh synthesis and instead a newly described class of choline transporters, the choline transporter-like proteins (CTL1 - 5), can mediate ACh synthesis. Therefore non-neuronal ACh synthesis in the lung may potentially be targeted without effecting neuronal ACh synthesis by targeting the correct CTL. To test this we propose these specific aims: (1) Identification of which choline transporter-like proteins are involved in choline-uptake in lung non-neuronal cells. (2) Identification of which CTL is coupled to non-neuronal ACh synthesis in the lung. (3) To determine if knockdown of the CTL linked to ACh synthesis can block lung cell proliferation. These aims will be implemented using specific siRNAs to knock down CTLs in H82 small cell lung carcinoma cells as a model for pulmonary neuroendocrine cells and H520 squamous cell lung carcinoma cells as a model for airway epithelial cells. These studies will allow the targeting of non-neuronal ACh synthesis as a first step in developing new therapies for lung diseases.

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