Expression and Host Defense Mechanisms of Hear-Shock Protein 70 of Paragonimus miyazakii
| Project/Area Number |
10670228
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
寄生虫学(含医用動物学)
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| Research Institution | Shimane Medical University |
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Principal Investigator |
SHIWAKU Kuninori Shimane Medical University, Department of Environmental Medicine, Associate Professor, 医学部, 助教授 (10108384)
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| Co-Investigator(Kenkyū-buntansha) |
磯邊 顕生 島根医科大学, 医学部, 助手 (30232375)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Paragonimus miyazakii / heat-shock cognate 70 protein / antigen / immune attack / 遺伝子 / cDNA |
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| Research Abstract |
The three clones were 1,095-1,552bp with poly(A) tail and lacked their 5'ends. A consensus poly(A) addition signal AATAAA was seen in the 3'region downstream of only PMHSP3 from the stop codon TGA for all three clones. The coding region consists of 1,017-1,488 nucleotides, equivalent to 339-496 amino acids. The predicted amino acid sequence of these coding regions showed extensive homology with several members of the heat-shock protein 70 family from diverse organisms. These paper is the first report of heat-shock protein 70 as a antigen candidate of paragonimiasis.
Heat-shock protein 70 is important in normal cellular processes such as protein folding, assembly, disassembly and degradation. Heat-shock 70 protein migrate from the cytoplasm to the nucleus where they associate with polypeptides that form an insoluble complex at the increased temperature. At elevated temperatures nuclear proteins become partially denatured, exposing hydrophobic regions that tend to interact to form insolub
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le aggregates. By binding to the exposed hydrophobic surfaces, stress-70 proteins could be released from their association with nuclear proteins by addition of ATP. Researchers have further suggested that heat-shock protein 70 has a general affinity for denatured or damaged proteins and acts in concert with ubiquitin to target proteins for lysosomal degradation.
Heat-shock protein 70 also plays a major role in the immune response to the variety of parasitic infections. One possible role of heat-shock protein 70 is repair or removal of damaged parasite proteins caused by various immune mediators. In the case of helminths, this may involve lipid peroxidation and subsquent damage to membrane and enzyme systems via oxygen free radicals, direct assault on the integrity of limiting membranes by complement, or attack by a variety of granulocyte-derived cytotoxins or cytolysins.
The predicted amino acid sequence of these clones showed the highest degree of similarity (85%) to a constitutively expressed heat-shock cognate 70 protein isolated from human in the heat-shock protein 70 family. These three clones are related to cytoplasmic heat-shock protein 70 homologs and have no KDEL sequence which is C terminal endoplasmic reticulum retention sequence. Although many data would provide a plausible link between heat-shock protein function and the immune system, it does not mean that the heat-chock protein 70 itself would represent a valid target of immunity. There is no evidence for a peripheral location of heat-shock cognate 70 protein in helminths. But, heat-shock cognate 70 protein had an intracellular location in adult S. mansoni, concentrated particularly in tegmental cells. Previous studies of the serum antibody response in mice to Mesocestoides corti infection indicated that molecules released by the parasite influenced the production of IgM and IgG1 to the exclusion of other isotypes. Two proteins isolated from M. corti culture supernatants were found to be homologous to the 70-kDa heat shock proteins (hsp70) and Escherichia coli GroEL families of stress proteins. These reports suggest that cytoplasmic heat-shock cognate 70 protein in the tegment of Paragonimus would release by non-specific immune attack, then be recognized as antigens by the host. Less
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Report
(3 results)
Research Products
(7 results)
