TRPC1, Calcium, and Saliva Secretion

TRPC1、钙和唾液分泌

• 批准号: 10577868
• 负责人: Brij B Singh
• 金额: $ 53.07万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10577868
• 关键词: Acinar Cell; Adenoviruses; Affect; Agonist; Autoantibodies; Award; Biological Process; Calcium; Calcium Channel; Caveolins; Cell Death; Cell membrane; Cells; Chloride Channels; Complex; Data; Deglutition; Disease; Drug Side Effects; Etiology; Event; Fluids and Secretions; Functional disorder; Goals; Grant; Human; IL14 gene; Immune response; Inflammatory; Ion Channel; Mastication; Mediating; Membrane Microdomains; Molecular; Mus; Oral; Oral cavity; Oral health; Pathologic; Pathway interactions; Patients; Persons; Pharmacotherapy; Phenotype; Play; Population; Positioning Attribute; Potassium; Potassium Channel; Proteins; Publishing; Regulation; Research; Role; Route; STIM1 gene; Saliva; Salivary Glands; Sampling; Signal Transduction; Sjogren' s Syndrome; Small Interfering RNA; Sodium-Potassium-Chloride Symporters; Speech; Taste Perception; Testing; Tissues; Up-Regulation; cytokine; endoplasmic reticulum stress; functional restoration; immune activation; immune cell infiltrate; insight; knock-down; mouse model; novel therapeutics; protein complex; protein protein interaction; receptor; recruit; response; saliva secretion; salivary cell; sensor; soft tissue; symporter; targeted treatment; tool; water channel

Project Summary Saliva is essential for several biological functions that are instrumental in maintaining oral health. It has been estimated that more than 5 million people in the US suffers from salivary gland dysfunction. Although saliva secretion is driven by concerted activities of several ion channels and transporters, the molecular mechanism involved in stimulated saliva secretion is not clearly understood. It has been suggested that Ca2+ plays a central role that regulates fluid secretion; however, information regarding the identity of the Ca2+ channels as well as the mechanism of regulation of these channels in salivary glands is not well understood. Moreover, in salivary gland dysfunction, such as primary Sjogren's syndrome (pSS) patients the acinar tissues appear to be normal but fail to function properly and have a decreased calcium response to agonist-stimulation. This observation raises the possibility that Ca2+ channels might be altered in this pathological condition. Results obtained from our awarded grant indicate that TRPC1 is the primary Ca2+ channel in salivary glands and is intimately involved saliva secretion. To understand the regulation of TRPC1 channel we have shown that TRPC1 is regulated through a complex protein-protein interaction. Furthermore, these interactions were confined to specific domains in the plasma membrane, but the protein that anchors these complexes is not clear. Therefore, in this renewal we intend to thoroughly characterize the role of cytosolic Ca2+ in salivary gland function and to determine the relationship between TRPC1 and salivary gland dysfunctions. The objective of this competitive renewal is to elucidate the Ca2+ signaling mechanism(s) in salivary gland dysfunction and establish the role of TRPC1 in pSS. This renewal application is based on the hypothesis that loss of TRPC1-mediated Ca2+ influx induces ER stress, promotes immune infiltration that leads to salivary gland destruction. The results of our studies are expected to provide new insights into the role of calcium channels and the molecular mechanism involved in salivary gland dysfunction as well as ways to restore functional salivary glands. Greater understanding of these events will be important in elucidating new therapy for salivary gland dysfunctions.

项目概要 唾液对于多种有助于维持口腔健康的生物功能至关重要。它有 据估计，美国有超过 500 万人患有唾液腺功能障碍。虽然 唾液分泌是由多个离子通道和转运蛋白的协同活动驱动的，分子 刺激唾液分泌的机制尚不清楚。有人建议 Ca2+ 在调节体液分泌方面发挥着核心作用；然而，有关该人身份的信息 唾液腺中Ca2+通道以及这些通道的调节机制尚不清楚 明白了。此外，在唾液腺功能障碍中，例如原发性干燥综合征（pSS）患者 腺泡组织看似正常，但无法正常发挥作用，并且钙反应降低 激动剂刺激。这一观察结果提出了 Ca2+ 通道可能在此过程中发生改变的可能性。 病理状况。从我们授予的资助中获得的结果表明 TRPC1 是主要的 Ca2+ 唾液腺中的通道，与唾液分泌密切相关。为了解监管 TRPC1 通道 我们已经证明 TRPC1 通过复杂的蛋白质-蛋白质相互作用进行调节。 此外，这些相互作用仅限于质膜中的特定区域，但蛋白质 锚定这些复合体的机制尚不清楚。因此，在这次更新中，我们打算彻底描述 细胞质 Ca2+ 在唾液腺功能中的作用并确定 TRPC1 和 唾液腺功能障碍。此次竞争性更新的目的是阐明 Ca2+ 信号传导 唾液腺功能障碍的机制并确定 TRPC1 在 pSS 中的作用。此次续订 该应用基于以下假设：TRPC1 介导的 Ca2+ 内流的丧失会诱导 ER 应激， 促进免疫浸润，导致唾液腺破坏。我们的研究结果是 有望为钙通道的作用及其分子机制提供新的见解 唾液腺功能障碍以及恢复唾液腺功能的方法。更深入地了解 这些事件对于阐明唾液腺功能障碍的新疗法非常重要。

项目成果

Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1.

Caveolin-1 通过调节 TRPC1 的质膜定位来促进钙池操纵的 Ca2 流入通道的组装。

• 发表时间: 2003-07-18
• 作者: Brazer, So;Singh, Brij B;Liu, Xibao;Swaim, William;Ambudkar, Indu S
• 通讯作者: Ambudkar, Indu S

Effect of cell swelling on ER/PM junctional interactions and channel assembly involved in SOCE.

细胞肿胀对 ER/PM 连接相互作用和 SOCE 中涉及的通道组装的影响。

• 发表时间: 2010-06
• 影响因子: 4
• 作者: Liu, Xibao;Ong, Hwei Ling;Pani, Biswaranjan;Johnson, Katherine;Swaim, William B;Singh, Brij;Ambudkar, Indu
• 通讯作者: Ambudkar, Indu

Physiological Function and Characterization of TRPCs in Neurons.

神经元中 TRPC 的生理功能和特征。

• 发表时间: 2014-05-21
• 影响因子: 6
• 作者: Sun, Yuyang;Sukumaran, Pramod;Bandyopadhyay, Bidhan C;Singh, Brij B
• 通讯作者: Singh, Brij B

Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway.

白藜芦醇通过下调 STIM1 和 mTOR 通路来激活前列腺癌细胞的自噬性细胞死亡。

• 发表时间: 2016-05
• 影响因子: 4.6
• 作者: Selvaraj, Senthil;Sun, Yuyang;Sukumaran, Pramod;Singh, Brij B
• 通讯作者: Singh, Brij B

Cytoskeletal reorganization internalizes multiple transient receptor potential channels and blocks calcium entry into human neutrophils.

细胞骨架重组内化多个瞬时受体电位通道并阻止钙进入人中性粒细胞。

• 发表时间: 2004-01-01
• 作者: Itagaki, Kiyoshi;Kannan, Kolenkode B;Singh, Brij B;Hauser, Carl J
• 通讯作者: Hauser, Carl J