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REGULATION OF MUSCLE GENE EXPRESSION IN TRICHINOSIS

旋毛虫病肌肉基因表达的调控

基本信息

批准号：
3454627
负责人：
DOUGLAS P JASMER
金额：
$ 9.55万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 1994-03-31
项目状态：
已结题

项目摘要

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。主要由受感染的猪肉引起。这种病会引起剧烈的疼痛有时会导致感染者死亡。幼虫感染旋毛虫线虫的致病作用引起了哺乳动物肌肉的形态、超微结构和生化方面的。几个变化表明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的增殖，如细胞核、线粒体、高尔基体和粗面内质网。然而，其他线粒体功能障碍等改变，以及胶原膜和溶酶体的增殖，这不同于再生肌肉，表明寄生虫主动改变正常的主机功能。描述这些变化的特征，展示了它们受到监管的程度，以及找出可能导致这些问题的寄生虫因素变化对于阐明1)的特征是重要的对寄生虫的生存至关重要的细胞；2) 负责改变宿主状态的机制；以及3)作用幼虫在决定寄主表型方面起着作用。获得这些目标可能导致新的方法来防止传播这种疾病。因为旋毛虫病的病理与其他肌肉寄生虫病和遗传病，获得答案对于旋毛虫病的这些问题可能适用于其他肌肉疾病。为了探讨这些问题，假设旋毛虫感染肌肉具有再生性肌肉表型受寄生虫积极影响的病毒将通过完成以下具体目标： 1)确定感染肌肉的分化状态关于正常的和再生的肌肉。 2)确定肌肉的表达水平感染肌肉中的特定蛋白质基因发生了改变，例如转录、转录后或翻译后。 3)鉴定和鉴定位于宿主细胞。