MACROMOLECULES OF COCHLEAR NONSENSORY TISSUES & FLUIDS

耳蜗非感觉组织的大分子

• 批准号: 2126445
• 负责人: ISOLDE THALMANN
• 金额: $ 23.8万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2126445
• 关键词: SDS polyacrylamide gel electrophoresis; biomechanics; chickens; cochlea; collagen; cytoskeletal proteins; ear hair cell; endolymph; extracellular matrix proteins; glycoproteins; guinea pigs; histology; in situ hybridization; laboratory mouse; nucleic acid probes; protein sequence

It is the general objective of this proposal to study the macromolecular makeup of the accessory structures bounding the cochlear duct - the tectorial and basilar membranes, spiral ligament, and spiral limbus - and the respective fluids in the mammal, and of the tectorial and basilar membranes in the bird. Of the fluids, endolymph will be given special attention. The macromolecules studied are collagens, proteoglycans, and glycoproteins, which form the major structural elements of the extracellular matrix of connective tissue. Interactions between these macromolecules in tissues and surrounding fluids determine their specific and unique properties. The sampling technique permits isolation of discrete cochlear structures and uncontaminated inner ear fluids. Highly sensitive biochemical and immunochemical techniques (including two-dimensional gel electrophoresis and amino acid sequencing) will be used, and molecular biologic in vitro and in situ studies will be conducted. The biochemical and molecular biologic features of these unique tissues, integrated with existing structural and biophysical knowledge, will provide better understanding of cochlear biomechanics, and will give insight into the processes involved in regeneration of avian hair cells and supporting structures. Most studies on auditory function treat the inner ear as a purely physical system; however, the effectors of the mechanical processes are living cells, and biochemical changes are the basis of the majority of pathological conditions. Genetic disorders of collagen metabolism (e.g. osteogenesis imperfecta, Marfan's syndrome, and Alport's syndrome) and glycosaminoglycans (mucopolysaccharidoses such as Hurler's syndrome and Hunter's syndrome) all result in impairment of auditory function. It is readily conceivable that the tectorial and/or basilar membranes, which both consist primarily of collagen and glycosaminoglycans, are involved in these disorders. In addition, changes of connective tissue occurring with age could be one of the dysfunctions involved in presbycusis.

研究大分子是这项建议的总目标。 环绕耳蜗管的附属结构的组成--耳蜗管 覆盖膜和基底膜、螺旋韧带和螺旋角膜缘--以及 哺乳动物的体液，以及盖骨和基底的体液 鸟体内的膜。在液体中，内淋巴将被给予特殊的 请注意。所研究的大分子是胶原蛋白、蛋白多糖和 糖蛋白，它构成了细胞的主要结构元素 结缔组织的细胞外基质。它们之间的相互作用 组织和周围液体中的大分子决定了它们的特异性 和独一无二的特性。 采样技术允许分离离散的耳蜗结构 和未受污染的内耳分泌物。高度敏感的生化和 免疫化学技术(包括双向凝胶电泳法 和氨基酸测序)，并在体外进行分子生物学 并将进行现场研究。 这些独特组织的生化和分子生物学特征， 结合现有的结构和生物物理知识，将 提供对耳蜗生物力学的更好理解，并将给出 洞察鸟类毛细胞再生的过程 和支撑结构。 大多数关于听觉功能的研究都将内耳作为一种纯粹的 物理系统；然而，机械过程的执行器是 活细胞和生化变化是大多数 病理情况。遗传性胶原代谢紊乱(如 成骨不全、马凡氏综合征和阿尔波特综合征)和 糖胺多聚糖(粘多糖病，如Hurler综合征和 亨特氏综合征)都会导致听觉功能受损。它是 不难想象，覆盖层和/或基底膜， 两者主要由胶原蛋白和糖胺聚糖组成，均参与其中 在这些障碍中。此外，结缔组织也发生了变化 随着年龄的增长，可能是老年性耳聋的功能障碍之一。