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.

唾液腺功能在维持正常的口腔健康以及在适当消化中起关键作用方面很重要。正常的唾液腺功能和稳态取决于细胞生长的平衡，细胞分化和细胞死亡的维持。美国数百万人患有主要和小唾液腺的良性和恶性肿瘤以及唾液腺功能障碍。唾液腺功能低下可能是由慢性药物治疗引起的，尤其是在老年人，Sjorgen综合征，一种自身免疫性疾病，X射线照射和癌症化学疗法中。在这些疾病条件下的每一个中，唾液腺功能可能会因腺泡细胞的丧失或由于异常细胞凋亡而导致的腺体稳态丧失而受到损害。该计划项目的远距离目标是提供基本信息，这些信息是完全了解分子水平上唾液腺泡凋亡所必需的。这种基本科学信息的发展对于理解唾液腺肿瘤发育的分子基础以及开发新的治疗方式，以治疗预防由异常细胞凋亡引起的唾液腺功能障碍。项目ONE将评估caspase和Bcl-2超家族在唾液腺泡凋亡中的作用。项目第二将评估MAPK和AKT信号转导途径在调节腺泡凋亡中的作用。第三项目将研究调节蛋白的蛋白激酶C家族在抑制和/或增强遗传毒性剂和凋亡的发作中的作用。对细胞内信号转导途径以及唾液腺泡凋亡的发起人和效应的重要性的基本理解是开发新的治疗策略来治疗唾液腺肿瘤性超官方在肿瘤发育中的第一步。

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