2003 Fiscal Year Final Research Report Summary
Molecular mechanisms of glucose transporter alterations and apoptosis progression in intestinal parasitoses
| Project/Area Number |
13470057
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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 |
寄生虫学(含医用動物学)
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
ARIZONO Naoki Kyoto Prefectural University of Medicine, Department of Medical Zoology, Professor, 医学研究科, 教授 (10079725)
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| Co-Investigator(Kenkyū-buntansha) |
TEGOSHI Tatsuya Kyoto Prefectural University of Medicine, Department of Medical Zoology, Assistant, 医学研究科, 助手 (40254370)
UCHIKAWA Ryuichi Kyoto Prefectural University of Medicine, Department of Medical Zoology, Assistant, 医学研究科, 助手 (80145466)
YAMADA Minoru Kyoto Prefectural University of Medicine, Department of Medical Zoology, Lecturer, 医学研究科, 講師 (70106392)
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| Project Period (FY) |
2001 – 2003
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| Keywords | intestinal parasite / malabsorption / apoptosis / granzyme / Nippostrongylus / glucose transporter / SGLT1 / GLUT5 |
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| Research Abstract |
To determine the cause of malabsorption in intestinal parasitoses, pathological alterations in the intestinal absorptive cells were examined in rats infected with the nematode Nippostrongylus brasiliensis. Nematode infection induced cytopathic alterations and enhanced apoptosis in the intestinal epithelial cells together with the development of villus atrophy. Studies in athymic rnu/rnu and mast cell-deficient Ws/Ws rats revealed that progression of the villus atrophy was dependent on T cells, but not on mast-cell activation, and its occurrence was associated with the increase in number of granzyme B-positive cells in the epithelium and the propria mucosa. T cell-independent cytopathic change was also found, that was possibly associated with TNF up-regulation. In addition, in-vitro studies clarified that N. brasiliensis worms produced and secreted a factor that could induce up-regulation of Fas and apoptosis in the intestinal epithelial cell line IEC-6. N. brasiliensis infection induced hypoglycemia and hypoalbuminemia, and these alterations were associated with decreased expression of glucose transporters SGLT1 and GLUT5,the peptide transporter PepT1,and the amino acid transporter LAT2 in the absorptive cells. These results indicated that nematode infection induces T cell-dependent and -independent apoptosis and cytopathic alterations in the intestinal absorptive cells together with decreased expression of transporter molecules, that could deteriorate nutrient absorption.
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