| Project/Area Number |
17390123
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Juntendo University |
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Principal Investigator |
AOKI Takashi Juntendo University, SCH. MED, PROFESSOR (20053283)
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| Co-Investigator(Kenkyū-buntansha) |
NARA TAKESHI JUNTENDO UNIVERSITY, SCH. MED, ASSIST PROFESSOR (40276473)
HASHIMOTO Muneaki JUNTENDO UNIVERSITY, SCH. MED, ASSOC. PROFESSOR (30407308)
ANNOURA TAKESHI JUNTENDO UNIVERSITY, SCR MED, ASSIST PROFESSOR (90407239)
TSUBOUCHI AKIKO JUNTENDO UNIVERSITY, SCH. MED, ASSIST PROFESSOR (10398662)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,550,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | TRYPANOSOMA CRUZI / INFECTED HUMAN CELLS / INHIBITION OF APOPTOSIS / UBIQUITINATION OF cFLIP / CHAGAS' DISEASE / PYRIMIDINE -BIOSYNTHETIC GENE CLUSTER / TRANSCRIPTOME / UPREGULATION OF PROLIFERATION INHIBITORS / ACT-DHOD融合遺伝子 / 翻訳後プロセッシング / ピリミジン合成遺伝子 / 遺伝子の起原と分子進化 / マイクロアレイ / 増殖抑制遺伝子のuregulation / 増殖促進遺伝子のdownregulation / リアルタイムPCR / 増殖促進因子のdownregulation / 増殖抑制因子のupregulation / cFLIPのユビキチン化 / cDNAチップ / c-FLIP / 原虫の生残り / 塩基置換頻度(SNPs) / 海草抽出物 |
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| Research Abstract |
Intracellular persistence of the protozoan parasite, Trypanosoma cruzi, is an aggravating cause of Chagas' disease, involving that the protozoan infection specifically inhibits death receptor-mediated apoptosis of host cells. We previously demonstrated that the parasite dramatically upregulates cellular FLICE inhibitory protein (cFLIP) , the only known mammalian inhibitor specific for death receptor signaling, in infected cells. While T cruzi infected cells had an expression level of Itch which is suggested to be an ubiquitin ligase for cFLIPL equivalent to that in uninfected cells, co-immunoprecipitation analysis revealed that the interaction between cFLIPL and Itch is strongly inhibited in T cruzi infected cells. This unique parasite strategy, which has not been reported in any pathogen-infected cells, may allow the host cell to accumulate cFLIPL, eventually resulting in the inhibition of apoptosis of T cruzi infected cells.
Upon an exhaustive transcriptome analysis of T cruzi infected HeLa cells in comparison with uninfected cells, the former showed >3-fold up-regulation of 41 genes and >3-fold down-regulation of 23 genes. Among these genes, seven up-regulated genes encode proliferation inhibitors and three down-regulated genes encode proliferation promoters, strongly. Suggesting that T cruzi infection inhibits host cell proliferation, which may allow more time for T cruzi to replicate and produce its intracellular nests.
In the diplonemid Diplonema papillatum that belongs to the sister group of kinetoplastids, phylogenetic analyses of pyr4 and pyr6 genes showed the separate origin of each in kinetoplastids and euglenoids/diplonemids and suggested that kinetoplastids have acquired these genes via lateral gene transfer. Taken together, we expect that the progress in the present study on "Trypanosoma cruzi: Molecular bases for intracellular parasitism, proliferation, and pathogenicity" would be extended to an applied study in near future.
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