Molecular analysis of excretory-secretory products of Trichinella causing muscle cell transformation.
Project/Area Number |
15590366
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Parasitology (including Sanitary zoology)
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Research Institution | Gifu University |
Principal Investigator |
NAGANO Isao Gifu University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (40283296)
|
Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yuzo Gifu University, School of Medicine, Professor, 医学部, 教授 (80094580)
WU Zhiliang Gifu University, Graduate School of Medicine, Research Associate, 大学院・医学研究科, 助手 (90313874)
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Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
Keywords | Trichinella / Gene expression / Cyst formation / Excretory-secretory products / Enolase / Nurse cell / Microarray / apoptosis / RCD-1 / nurse cell / ミトコンドリア |
Research Abstract |
Infection with Trichinella spiralis or T.pseudospiralis causes muscle cell transformation and satellite cell proliferation, and T.spiralis forms typical cyst but T.pseudospiralis forms very poor cyst. We established two clones encoding the T.pseudospiralis excretory-secretory proteins related to the T.spiralis proteins, and revealed that these two proteins are important for muscle cell transformation, cyst formation and continuation of parasitism due to Trichinella. The nurse cell in the cyst of T.spiralis comprises at least two kinds of cytoplasm, derived from muscle or satellite cells. We revealed that the nurse cell cytoplasm differed between the two Trichinella species and between the two origins of cytoplasm in the cyst of T.spiralis. A time course study was performed to reveal the sequence of histopathology after T.spiralis or T.pseudospiralis infection in mice. A cyst was formed in the former case by about 18 days post infection and prominent myopathy was restricted within the cy
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st. In the latter case, however, no typical cyst was formed, and myopathy spread diffusely over the infected muscle tissues occupying half area of muscle sections. To search for the candidate genes responsible for nurse cell formation, cDNA microarray analysis of muscle tissues was performed before and after Trichinella infection. After the infection, several genes increased expression, and these genes after the infection responsible for cell differentiation, proliferation, cell cycle and apoptosis. The expression of mitochondrial apoptosis related genes is elevated in Trichinella spiralis-infected muscles during encapsulation. These were expressed in the basophilic cytoplasm (infected muscle cell origin) of the nurse cells. The infected muscle cells transform but die through the process of apoptosis, which is triggered by factors from the newly formed mitochondria. The anti-apoptosis factor may help the eosinophilic cytoplasm with its survival to ensure nurse cell function. The expression of the factors of TNF-α/TNF receptor 1 signaling pathway mediating apoptosis was investigated. The infected muscle tissues up-regulate the expression of proapoptosis genes, and anti-apoptosis genes at the beginning of cyst formation. The expression returned to the normal level after cyst formation. We established a cDNA clone from the cDNA library constructed from Trichinella spiralrs. A cDNA clone, encoded enolase that catalyzed a reversible conversion of 2-phospho-D-glyceric acid to phosphoenolpyruvate in the glycolytic pathway. Less
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Report
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Research Products
(21 results)