1997 Fiscal Year Final Research Report Summary
Significance of Reactive Oxygen Intermediates in Fas-mediated apoptosis.
| Project/Area Number |
08670862
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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 |
Pediatrics
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| Research Institution | Kanazawa University |
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Principal Investigator |
KASAHARA Yoshihito Kanazawa University, School of Medicine, Dept.of Pediatrics, Associate Professor, 医学部・小児科学教室, 助教授 (30204366)
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| Project Period (FY) |
1996 – 1997
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| Keywords | apoptosis / reactive oxygen intermediates / Fas / neutrophil / autoimmune lymphoproliferative syndrome / Fas mutation |
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| Research Abstract |
1) The involvement of reactive oxygen intermediates in Fas-mediated apoptosis was investigated using cells from patients with chronic granulomatous disease (CGD) that have no ability of reactive oxygen intermediates production. Although the treatments with anti-Fas antibody induced apoptosis of cells from normal subjects, cells from CGD were resistant to anti-Fas antibody. Catalase significantly inhibited Fas-mediated apoptosis of normal cells, on the other hands hydrogen peroxides induced apoptosis of CGD cells.
2) Fas-mediated apoptosis was estimated in two siblings with autoimmune lymphoproliferative syndrome characterized with hepatosplenomegaly, lymphadenopathy, pancytopenia, hyper-gammagloblinemia, which is similar to clinicalmanifestations of lpr or gld mouse that have mutations of Fas or Fas ligand gene. Cells from two patients showed reduced Fas-induced apoptosis and smaller abnormal Fas protein was detected by western blot analysis. The T to C point mutation of intron 7 in patients Fas gene was detected and Fas antigen of patients lacks intracellular portion including death domain by this mutation TCRalphabeta+CD4-CD6- T cells were increased in blood I patients and analysis of family showed that mother has a same Fas mutation. These results indicated significance of Fas-mediated apoptosis in immunological homeostasis n vivo.
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Research Products
(11 results)
