2006 Fiscal Year Final Research Report Summary
Molecular mechanism of leukocyte activation by galectin via integrin family
| Project/Area Number |
17570116
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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 |
Functional biochemistry
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| Research Institution | Kagawa University |
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Principal Investigator |
NAKAMURA Takanori Kagawa University, Faculty of medicine, Professor, 医学部, 教授 (70183887)
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| Co-Investigator(Kenkyū-buntansha) |
NISHI Nozomu Kagawa University, School of medicine, Assistant, 医学部, 助手 (10145047)
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| Project Period (FY) |
2005 – 2006
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| Keywords | galectin / galectin-9 / immune system / Jurkat / cell adhesion / cell death / apoptosis / caspase |
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| Research Abstract |
Galectins are members of an animal lectin family, which specifically recognizes P-galactoside structure of glycoconjugates. In this study, we attempted to analyze the molecular mechanism of the functions and their signaling of tandem repeat galectins, such as galectins-8 and-9 in immune cells. First, we compared the effects of galectins-8 and-9on the apoptosis and cell adhesion in various immune cell lines. Galectin-9 induced apoptosis of Tell lines (Jurkat and Molt-4), but galectin-8 did not Both of galectins mediated the cell adhesion to plastic culture plates in B-cell lines(Namalwa, and RPM-8866) and a monocytic cell (THP-1) in addition of T-cell lines. In the present study, we examined the properties of galectin-9-mediated cell death of Jurkat T-cells. Galectin-9NC (wild-type), consisting of two CRDs (N-terminal and C-terminal carbohydrate recognition domains), and derivatives of it, galectins-9-NN and-9-CC, induced Jurkat T-cell apoptosis. However, a single CRD (galectin-9NT or-CT) had no effect, suggesting the stable dimeric structure of two CRDs is required for the activity. The apoptosis was inhibited by pretreatment with an N-glycan synthesis inhibitor, indicating that the expression of N-glycans in the cells is essential for galectin-9-induced apoptosis. We previously showed that the apoptosis of MOLT-4 cell is mediated by galectin-9 via a Ca^<2+>-calpain-caspase-1-dependent pathway. In Jurkat cells, the cell death by galectin-9, was insufficiently suppressed by caspase inhibitors, Ca^<2+>-chelator or calpain inhibitor. Furthermore, we observed the loss of mitochondrial membrane potential and significant AIF release in galectin-9-treated cells. These findings suggest that caspase-dependent and-independent death pathways exist in Jurkat cells, and the main pathway might vary with the T-cell type.
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Research Products
(8 results)
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[Journal Article] Carbohydrate-recognition domains of galectin-9 are involved in intermolecular interaction with galectin-9 itself and other members of the galectin family.2007
Author(s)
N.Miyanishi, N.Nishi, H.Abe, Y.Kashio, R.Shinonaga, S.Nakakita, W.Sumiyoshi, A.Yamauchi, T.Nakamura, M.Hirashima, J.Hirabayashi
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Journal Title
Glycobiology 17
Pages: 423-432
Description
「研究成果報告書概要(欧文)」より
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