MOLECULAR MECHANISMS REGULATING CALCIUM FLUX IN SALIVARY GLANDS

调节唾液腺钙通量的分子机制

• 批准号: 2572327
• 负责人: I S AMBUDKAR
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2572327
• 关键词: affinity chromatography; basolateral membrane; calcium channel; calcium flux; chronic disease /disorder; inflammation; phosphoproteins; radiobiology; salivary glands; tissue /cell culture; vesicle /vacuole

Fluid secretion in salivary glands is regulated by a sustained elevation of cytoplasmic [Ca2+], which is primarily due to influx. The Ca2+ entry mechanism in salivary gland, and other non-excitable, cells has not yet been determined. This project is directed towards understanding the processes that mediate and regulate Ca2+ influx in salivary gland cells. In this reporting period we have demonstrated that protein (Ser/Thr) phosphorylation is involved in a feedback modulation of Ca2+ influx by Ca2+. Further, we have identified the low affinity Ca2+ influx component as the site of this modulation. We have now demonstrated that isolated basolateral plasma membrane vesicles contain two Ca2+ influx pathways similar to those detected intact parotid acinar cells. Continuing our efforts to purify the proteins involved in these Ca2+ influx pathways, we have used lectin affinity chromatography to partially purify a calcium-permeable cation channel from basolateral plasma membrane vesicles. We have also continued our efforts to understand the damage induced in salivary glands by pathological conditions such as irradiation and chronic inflammation. The physiological status of the damaged cell as well as the possible mechanisms of damage are being investigated. These studies will help CIPCB efforts to devise therapeutic procedures for the recovery of salivary gland function.

唾液腺中的液体分泌受持续的调节 细胞质[Ca2+]的升高，主要是由于流入。 唾液腺中的Ca2+进入机制和其他不可启示的 细胞尚未确定。 这个项目针对 了解介导和调节Ca2+涌入的过程 唾液腺细胞。 在此报告期内，我们已经证明了 反馈参与该蛋白（Ser/Thr）磷酸化 Ca2+的Ca2+涌入调制。 此外，我们已经确定了 低亲和力Ca2+涌入成分作为此调制的位点。 我们现在证明了孤立的基底外侧质膜 囊泡包含两个CA2+涌入途径，类似于检测到的途径 完整的腮腺细胞。 继续努力净化 涉及这些Ca2+流入途径的蛋白质，我们使用了凝集素 亲和力色谱法部分纯化钙可渗透 基底外侧质膜囊泡的阳离子通道。 我们有 也继续我们努力了解造成的损害 唾液腺受辐射和诸如辐照和 慢性炎症。 受损细胞的生理状态 以及可能的损害机制。 这些研究将有助于CIPCB努力设计治疗 恢复唾液腺功能的程序。