REGULATION OF MUSCLE GENE EXPRESSION IN TRICHINOSIS

旋毛虫病肌肉基因表达的调控

• 批准号: 3454624
• 负责人: DOUGLAS P JASMER
• 金额: $ 8.37万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3454624
• 关键词: Trichinella; anthelmintics; autoradiography; cell differentiation; complementary DNA; creatine kinase; disease /disorder prevention /control; electron microscopy; enzyme mechanism; gel electrophoresis; gene expression; gene mutation; genetic regulation; host organism interaction; isozymes; laboratory mouse; laboratory rabbit; laboratory rat; larva; microscopy; molecular pathology; morphology; muscle cells; muscle disorders; muscle proteins; myogenesis; nucleic acid hybridization; nucleic acid probes; organelles; regeneration; trichinosis

Trichinosis is a parasitic disease transmitted to humans predominately by infected pork. This disease causes severe pain and sometimes death to infected individuals. Infection by larvae of the nematode Trichinella spiralis causes dramatic changes in mammalian muscle morphologically, ultrastructurally, and biochemically. Several alterations suggest that infected muscle is suspended in a regenerative muscle phenotype. These include the proliferation of various organelles such as nuclei, mitochondria, golgi apparatus and rough endoplasmic reticulum. However, other alterations such as mitochondrial dysfunctions, and the proliferation of a collagen capsule and lysosomes, which are unlike regenerative muscle, suggest that the parasite actively alters normal host function. Characterizing these alterations, demonstrating the level at which they are regulated, and identifying parasite factors that may be responsible for these changes is important for elucidating 1) the characteristics of the cell that are important for survival of the parasite; 2) the mechanisms responsible for the altered host state; and 3) the role that the larva plays in determining the host phenotype. Attaining these goals could lead to novel methods to prevent transmission of the disease. Since the pathology of trichinosis has similarities to other parasitic and genetic diseases of muscle, obtaining answers to these questions for trichinosis may have application to other muscle diseases. To approach these questions, the hypothesis that T. spiralis infected muscle has a regenerative muscle phenotype which is actively influenced by the parasite will be tested by completing the following specific aims: 1) Determine the state of differentiation of the infected muscle with regard to normal and regenerative muscle. 2) Determine the level at which the expression of the muscle specific protein genes are altered in infected muscle, e.g. transcription, posttranscription or posttranslation. 3) Identify and characterize larval proteins that are located in the host cell.

旋毛虫病是一种传染给人类的寄生虫病 主要是受感染的猪肉。 这种病会引起剧烈的疼痛 有时甚至会导致感染者死亡。 幼虫感染 旋毛虫线虫的感染会引起 哺乳动物肌肉形态学，超微结构，和 生物化学 一些变化表明，受感染的肌肉是 悬浮在再生肌肉表型中。 其中包括 各种细胞器如细胞核，线粒体， 高尔基体和粗面内质网。 但其他 改变，如线粒体功能障碍，以及 胶原蛋白囊和溶酶体的增殖，这与 再生肌肉，表明寄生虫主动改变 正常的主机功能。 描述这些变化， 表明其受监管的程度，以及 确定可能导致这些疾病的寄生虫因素 变化是重要的阐明1）的特点 对寄生虫的生存很重要的细胞; 2） 负责改变宿主状态的机制;以及3）作用 幼虫在决定宿主表型方面的作用。 实现 这些目标可能会导致新的方法，以防止传播 这种疾病 由于旋毛虫病的病理学与 肌肉的其他寄生虫和遗传疾病，获得答案 旋毛虫病的这些问题可能适用于其他 肌肉疾病。 为了解决这些问题，假设 T.感染旋毛虫的肌肉具有再生肌肉表型 受寄生虫积极影响的细胞将被测试， 完成以下具体目标： 1)确定受感染肌肉的分化状态 关于正常和再生肌肉。 2)确定肌肉的表达水平 特定的蛋白质基因在受感染的肌肉中发生改变，例如， 转录、转录后或翻译后。 3)鉴定和表征位于 宿主细胞