MECHANISMS OF GROWTH AND ATROPHY OF SKELETAL MUSCLE

骨骼肌生长和萎缩的机制

• 批准号: 3394272
• 负责人: ALFRED L GOLDBERG
• 金额: $ 32.5万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-09-29 至 1989-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3394272
• 关键词: Escherichia coli; I cell disease; acidosis; adenosine triphosphate; alanine; aminoacid metabolism; bioenergetics; branched chain aminoacid; cell free system; chemical aggregate; fasting; glucocorticoids; glucose metabolism; glutamine; growth /development; hormone regulation /control mechanism; human tissue; insulin; liver cells; lysosomes; molecular pathology; muscle cells; muscle contraction; muscle disorders; muscle hypertrophy; muscle metabolism; muscle pharmacology; muscle proteins; nitrogen balance; nutrition related tag; peptidases; peritonitis; protease inhibitor; protein deficiency; proteolysis; radiotracer; reticulocytes; striated muscles; thyroid hormones; tissue /cell culture; trauma; uremias

The proposed research concerns the biochemical mechanisms regulating growth and atrophy of skeletal muscle. These investigations will attempt to clarify the cellular events through which physiological factors, such as the level of muscular work, dietary intake and hormones induce muscle growth or cause muscle atrophy. This work represents a continuation of earlier studies of the regulation of protein degradation, protein synthesis, and amino acid transport in muscle. A major objective of future research will be to learn more about the control, selectivity, and physiological importance of intracellular protein breakdown in muscle and other cells. Despite recent progress, our knowledge of the biochemical mechanisms of intracellular protein breakdown is still rudimentary. We hope to elucidate the pathways for intracellular proteolysis, to identify the responsible degradative enzymes in both mammalian and bacterial cells, and to clarify their modes of regulation. In particular, these studies will concern the role of lysosomal and nonlysosomal enzymes in the degradation of cell proteins and will investigate the very rapid breakdown of abnormal proteins as result from mutations or biosynthetic errors. Related studies will examine the control of amino-acid metabolism in skeletal muscle. Muscle is the major site in the body for degradation of the branched chain amino acids and for the production of alanine and glutamine. We hope to learn more about the physiological significance of these processes and to clarify their relationships to one another to the control of protein turnover in muscle, and to overall energy metabolism in the organism.

拟议的研究涉及调节生长和的生化机制 骨骼肌的萎缩。 这些调查将试图澄清 细胞事件通过其生理因素（例如 肌肉工作，饮食摄入和激素会诱导肌肉生长或引起肌肉 萎缩。 这项工作代表了早期研究的延续 蛋白质降解，蛋白质合成和氨基酸转运的调节 在肌肉中。 未来研究的主要目标是了解更多有关控制的信息， 细胞内蛋白质分解的选择性和生理重要性 肌肉和其他细胞。 尽管最近取得了进展，但我们对 细胞内蛋白质分解的生化机制仍然是基本的。 我们希望阐明细胞内蛋白水解的途径，以确定 哺乳动物和细菌细胞中的负责降解酶，以及 澄清他们的监管方式。 特别是这些研究将涉及 溶酶体和非酶体酶在细胞降解中的作用 蛋白质并将研究异常蛋白质的非常快速的分解 突变或生物合成误差引起的。 相关研究将检查骨骼中氨基酸代谢的控制 肌肉。 肌肉是体内降解的主要部位 链氨基酸以及用于丙氨酸和谷氨酰胺的生产。 我们希望 了解有关这些过程的生理意义的更多信息 澄清他们之间的关系以控制蛋白质周转 肌肉，以及生物体的总体能量代谢。