MOLECULAR MECHANISMS OF SALIVARY ACINAR CELL APOPTOSIS

唾液腺泡细胞凋亡的分子机制

• 批准号: 6738112
• 负责人: David O Quissell
• 金额: $ 106.93万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-15 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6738112
• 关键词: acinar cell; apoptosis; salivary glands

Salivary gland function is important in maintaining normal oral health, as well as playing a critical role in proper digestion. Normal salivary gland function and homeostasis is dependent upon the balance of cell growth, maintenance of cellular differentiation and cell death. Several million people in the United States suffer from benign and malignant tumors of the major and minor salivary glands and salivary gland hypofunction. Salivary gland hypofunction can be caused by chronic drug treatment, particularly in the elderly, Sjorgen's syndrome, an autoimmune disease, X-ray irradiation and cancer chemotherapy. In each of these disease conditions, salivary gland function may be compromised by the loss of the acinar cells or loss of glandular homeostasis due to aberrant apoptosis. The long range goal of this Program Project is to provide the fundamental information that is necessary to fully understand salivary acinar apoptosis at the molecular level. The development of such basic scientific information is essential in understanding the molecular basis of salivary gland tumor development and for the development of new therapeutic modalities for the treatment of prevention of salivary gland hypofunction caused by aberrant apoptosis. Project One will evaluate the role of the caspase and Bcl-2 superfamilies in salivary acinar apoptosis. Project Two will evaluate the role of the MAPK and Akt signal transduction pathways in regulating acinar apoptosis. Project Three will investigate the role of the protein kinase C family of regulatory proteins in suppressing and/or enhancing genotoxic agents and the onset of apoptosis. A fundamental understanding of how important intracellular signal transduction pathways along with the initiators and effectors of salivary acinar apoptosis is the first step in the development of new therapeutic strategies for the treatment of salivary gland hypofunction in neoplastic development.

唾液腺的功能在维持正常的口腔健康方面很重要，并且在适当的消化中发挥关键作用。正常的唾液腺功能和体内平衡依赖于细胞生长、细胞分化和细胞死亡的维持的平衡。在美国有数百万人患有大小唾液腺的良性和恶性肿瘤以及唾液腺功能减退。唾液腺功能减退可由慢性药物治疗引起，特别是在老年人中，Sjorgen综合征，一种自身免疫性疾病，X射线照射和癌症化疗。在这些疾病状况中的每一种中，唾液腺功能可能由于腺泡细胞的损失或由于异常细胞凋亡引起的腺稳态的损失而受损。本项目的长期目标是提供在分子水平上充分了解唾液腺泡凋亡所必需的基本信息。这些基本科学信息的发展对于理解唾液腺肿瘤发展的分子基础和开发用于治疗预防由异常细胞凋亡引起的唾液腺功能减退的新治疗模式是必不可少的。项目一将评估胱天蛋白酶和Bcl-2超家族在唾液腺泡凋亡中的作用。项目二将探讨MAPK和Akt信号转导通路在腺泡凋亡调控中的作用。项目三将研究蛋白激酶C家族调节蛋白在抑制和/或增强遗传毒性剂和细胞凋亡发生中的作用。对细胞内信号转导通路沿着唾液腺泡凋亡的启动子和效应子的重要性的基本理解是开发新的治疗策略以治疗肿瘤发展中的唾液腺功能减退的第一步。

项目成果

Suppression of radiation-induced salivary gland dysfunction by IGF-1.

• DOI: 10.1371/journal.pone.0004663
• 发表时间: 2009
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Limesand, Kirsten H.;Said, Sherif;Anderson, Steven M.
• 通讯作者: Anderson, Steven M.

Characterization of rat parotid and submandibular acinar cell apoptosis in primary culture.

原代培养中大鼠腮腺和下颌下腺泡细胞凋亡的特征。

• DOI: 10.1007/s11626-003-0012-1
• 发表时间: 2003
• 期刊: In vitro cellular & developmental biology. Animal
• 作者: Limesand,KirstenH;Barzen,KatherineA;Sanders,LindaA;Sclafani,RobertA;Raynolds,MaryV;Reyland,MaryE;Anderson,StevenM;Quissell,DavidO
• 通讯作者: Quissell,DavidO