ANALYSIS OF PAROTID GLAND 4B-GALACTOSYLTRANSFERASE

腮腺 4B-半乳糖基转移酶的分析

• 批准号: 3072226
• 负责人: MICHAEL G HUMPHREYS-BEHER
• 金额: $ 5.55万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3072226
• 关键词: Golgi apparatus; beta antiadrenergic agent; biomarker; carcinogenesis; cell adhesion; cell differentiation; cell growth regulation; cell membrane; complementary DNA; cyclic AMP; cytogenetics; enzyme induction /repression; enzyme mechanism; galactosyltransferases; genetic regulation; hyperplasia; hypertrophy; laboratory rat; membrane activity; molecular genetics; parotid gland

Chronic injections of beta-adrenergic agonist, agents that specifically raise intracellular cAMP levels and certain dietary changes, produce cell hypertrophy and hyperplasia in the rat parotid gland. Additionally, there is an increase in specific activity of the Golgi marker enzyme 4beta-galactosyltransferase. This change in activity is accompanied by an altered subcellular localization of this enzyme to the plasma membrane. The importance of up-regulation and surface localization became apparent in experiments in which agents that interact with this enzyme were shown to severely inhibit parotid gland cell hypertrophy and hyperplasia from taking place either in vitro or in vivo. Numerous reports have shown the alteration of cell surface Gal T'ase activity might be involved in cell adhesion, differentiation and tumorogenesis. Molecular studies on the regulation of the transferase, are crucial to understanding growth control in parotid and other tissues. Our basic understanding of salivary gland development and differentiation are guided by physiological and histological observations. My laboratory has provided new insights into the biochemical and molecular basis of acinar cell growth by having isolated a cDNA clone to 4beta-Gal T'ase. Our long-term goal is to understand the complex regulation of the Gal T'ase gene and how it mediates cell growth. The RCDA would allow me time to pursue several activities which would enhance my research development. During the course of the award, we propose to initiate collaborations with other salivary gland researchers with expertise in cell biology. One of our interests is the role Gal T'ase plays in developmental interactions with extracellular matrix and its contribution to cell migration. The RCDA would also allow me time for expanding my interactions with the faculty in the College of Dentistry. The pursuit of correlations in human pathologies of the oral cavity involving tissue hyperplasia will require close cooperation with the clinical and research faculty. These experiences would be extremely valuable and could be applied in my future studies of parotid gland growth and development.

长期注射β-肾上腺素能激动剂，这种药物专门 提高细胞内 cAMP 水平和某些饮食变化，产生 大鼠腮腺细胞肥大和增生。 此外，高尔基体的比活性增加 标记酶4β-半乳糖基转移酶。 这种活动的变化是 伴随着这种酶的亚细胞定位的改变 质膜。 上调和表面的重要性 本地化在实验中变得明显，在这些实验中，代理 与这种酶的相互作用被证明会严重抑制腮腺 细胞肥大和增生在体外或在体内发生 体内。 许多报告显示细胞表面Gal的改变 T'ase 活性可能参与细胞粘附、分化和 肿瘤发生。 转移酶调节的分子研究， 对于理解腮腺和其他部位的生长控制至关重要 组织。 我们对唾液腺发育的基本了解 分化受生理和组织学指导 观察。 我的实验室提供了新的见解 腺泡细胞生长的生化和分子基础 4beta-Gal T'ase 的 cDNA 克隆。 我们的长期目标是了解 Gal T'ase 基因的复杂调控及其如何介导细胞 生长。 RCDA 让我有时间从事多项活动 将促进我的研究发展。 在颁奖过程中， 我们建议与其他唾液腺开展合作 具有细胞生物学专业知识的研究人员。 我们的兴趣之一是 Gal T'ase 在细胞外发育相互作用中的作用 基质及其对细胞迁移的贡献。 RCDA 还将 让我有时间扩大与教授的互动 牙科学院。 追求人类病理学的相关性 涉及组织增生的口腔需要密切关注 与临床和研究人员的合作。 这些经历 将非常有价值，可以应用于我未来的研究 腮腺的生长和发育。