MOLECULAR BIOLOGY OF SALIVARY ACINAR CELL APOPTOSIS

描述：细胞凋亡，或程序性细胞死亡，是一个重要的组成部分， 正常的腺体发育和体内平衡在身体的所有组织 包括唾液腺腺泡细胞。 然而，对分子的研究 唾液腺泡细胞的凋亡机制受到阻碍， 缺乏体外细胞模型 可以操纵与糖尿病相关的基因，并评估其功能。 腮腺和颌下腺高分化腺泡细胞 线已经开发。 这些细胞系将用于本提案 开发稳定的唾液腺泡细胞系，其中表达 糖尿病相关蛋白可以被调节。 这些细胞系将 使用四环素（泰特）调节的基因表达系统产生。 在 首先制备表达泰特反式激活因子的该系统细胞系 蛋白（tTA）。 这些细胞系然后用一种抗肿瘤药物进行二次转染。 在tTA调节启动子控制下的靶基因。 的 靶蛋白的表达水平受浓度调节 泰特在细胞培养基中。 该提案的长期目标是 利用这些模型细胞系来确定特定细胞的作用， 唾液腺腺泡细胞凋亡的调节剂。 第一 待检测的前列腺增生相关靶基因是Bcl-2，已知其与前列腺增生相关。 抑制许多细胞进入凋亡途径。 这些细胞 线也将有广泛的应用，为研究的许多方面 唾液腺泡细胞生物学，因为它们可以用于调节 几乎任何靶蛋白的表达。 辐射和药物诱导的口干症，导致唾液腺泡细胞 功能障碍，是一个主要的口腔健康问题。 各种机制， 所有这些都有可能加速 唾液腺泡细胞凋亡，从而增强腺泡细胞的增殖。 功能障碍和口腔疾病。 对唾液腺的进一步了解 细胞凋亡及其调控具有开发新的 治疗模式，以阻止或干扰这些毒性作用 因此有助于维持或维持正常的唾液分泌 腺体功能

DESCRIPTION: Apoptosis, or programmed cell death, is an essential component of normal glandular development and homeostasis in all tissues of the body including salivary gland acinar cells. However, study of the molecular mechanism of apoptosis in salivary acinar cells has been hampered due to the lack of an in vitro cell model in which the expression of apoptosis-associated genes can be manipulated and their function evaluated. The highly differentiated parotid and submandibular salivary acinar cell lines have been developed. These cell lines will be used in this proposal to develop stable salivary acinar cell lines in which the expression of apoptosis-associated proteins can be regulated. These cell lines will be generated using the tetracycline (tet) regulated gene expression system. In this system cell lines are first made which express the tet transactivator protein (tTA). These cell lines are then secondarily transfected with a target gene which is under the control of a tTA regulated promoter. The level of expression of the target protein is regulated by the concentration of tet in the cell culture media. Th long term goal of this proposal is to utilize these model cell lines to determine the role of specific cellular modulators of apoptosis in salivary gland acinar cells. The first apoptosis-associated target gene to be examined is Bcl-2, a gene known to inhibit the entry of many cells into the apoptotic pathway. These cell lines will also have wide spread applications for the stud of many aspects of salivary acinar cell biology since they can be used for the regulated expression of virtually any target protein. Irradiation and drug-induced xerostomia, resulting in salivary acinar cell dysfunction, is a major oral health problem. A variety of mechanisms are likel to be involved, all of which have the potential of accelerating the salivary acinar cells into apoptosis, and thus enhancing glandular dysfunction and oral disease. A better understanding of salivary gland apoptosis and its regulation has the potential for the development of new treatment modalities to block or interfere with the toxic effects of these types of therapeutics and thus help to maintain or sustain normal salivary gland function.