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Molecular mechanism of leukocyte activation by galectin via integrin family

半乳糖凝集素通过整合素家族激活白细胞的分子机制

基本信息

批准号：
17570116
负责人：
NAKAMURA Takanori
金额：
$ 2.3万
依托单位：
Kagawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17570116/
关键词：
galectin galectin-9 immune system Jurkat cell adhesion cell death apoptosis caspase galectin-8 インテグリン CD45 integrinα4 リン酸化

项目摘要

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.

凝集素是动物凝集素家族的成员，它能特异性识别糖缀合物的p -半乳糖苷结构。在本研究中，我们试图分析免疫细胞中串联重复半乳糖凝集素-8和9的功能及其信号传导的分子机制。首先，我们比较了半乳糖凝集素-8和9对不同免疫细胞系细胞凋亡和细胞粘附的影响。半凝集素-9诱导Tell细胞系（Jurkat和Molt-4）的细胞凋亡，而半凝集素-8则无此作用。两种半凝集素均介导b细胞系（Namalwa和RPM-8866）和单核细胞（THP-1）与塑料培养板的粘附。在本研究中，我们检测了半乳糖凝集素-9介导Jurkat t细胞死亡的特性。由两个CRDs （n端和c端碳水化合物识别结构域）组成的半乳糖凝集素- 9nc（野生型）及其衍生物半乳糖凝集素-9- nn和9- cc诱导Jurkat t细胞凋亡。然而，单个CRD（半乳糖凝集素- 9nt或ct）没有影响，这表明两个CRD的稳定二聚体结构是活性所必需的。n-聚糖合成抑制剂预处理可抑制细胞凋亡，表明n-聚糖在细胞中的表达对半乳糖凝集素-9诱导的细胞凋亡至关重要。我们之前发现MOLT-4细胞的凋亡是由galectin-9通过Ca^<2+>-calpain-caspase-1依赖通路介导的。在Jurkat细胞中，caspase抑制剂、Ca^<2+>-螯合剂或calpain抑制剂不能充分抑制半乳糖凝集素-9引起的细胞死亡。此外，我们观察到半乳糖凝集素-9处理的细胞线粒体膜电位的丧失和显著的AIF释放。这些发现提示Jurkat细胞存在caspase依赖性和非依赖性死亡途径，主要途径可能因t细胞类型而异。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer

DOI：
10.1158/1078-0432.ccr-04-0861
发表时间：
2005-04-15
期刊：
CLINICAL CANCER RESEARCH
影响因子：
11.5
作者：
Irie, A;Yamauchi, A;Hirashima, M
通讯作者：
Hirashima, M

Crystal structure of the galectin-9 N-terminal carbohydrate recognition domain from MUS musculus reveals basic mechanism of carbohydrate recognition.

MUS musculus 半乳糖凝集素 9 N 末端碳水化合物识别结构域的晶体结构揭示了碳水化合物识别的基本机制。

DOI：
发表时间：
2006
期刊：
J. Biol. Chem. 281
影响因子：
0
作者：
佐藤ちひろ;北島健;佐藤ちひろ;Helle F.Jorgensen;Toru Sato;Yu-ichi Fujimura;遠藤充浩;Kyo-ichi Isono;Kyo-ichi Isono;L.-H.Lu et al.;N.Miyanishi et al.;M.Nagae et al.
通讯作者：
M.Nagae et al.

Carbohydrate-recognition domains of galectin-9 are involved in intermolecular interaction with galectin-9 itself and other members of the galectin family.

半乳糖凝集素 9 的碳水化合物识别域参与半乳糖凝集素 9 本身和半乳糖凝集素家族其他成员的分子间相互作用。

DOI：
发表时间：
2007
期刊：
Glycobiology 17
影响因子：
0
作者：
佐藤ちひろ;北島健;佐藤ちひろ;Helle F.Jorgensen;Toru Sato;Yu-ichi Fujimura;遠藤充浩;Kyo-ichi Isono;Kyo-ichi Isono;L.-H.Lu et al.;N.Miyanishi et al.
通讯作者：
N.Miyanishi et al.

ガレクチンの標的分子を捜せ

寻找半乳糖凝集素靶分子