Application of LIG gene to identify the early atherosclerotic lesions in human

应用LIG基因识别人类早期动脉粥样硬化病变

• 批准号: 15590495
• 负责人: YAMADA Shigeki
• 金额: $ 2.3万
• 依托单位: JICHI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590495/
• 关键词: LIG; HIP2; ubiquitination; atherosclerosis; monocytes; macrophages; apoptosis; TP-1 cells; foam cells(泡沫細胞); apoptosis(アポトーシス)

Under normoxic and hypoxic conditions, THP-1 cell-derived monocytes and macrophages express LIG/HIP2 proteins. Because the LIG/HIP2 protein expression was upregulated by hypoxia in monocytes, and there was minimal effect of hypoxia on the cell death of monocytes, LIG/HIP2 may have a protective role against the hypoxia-induced cell death of monocytes. The LIG/HIP2 protein profile and the association of the protein with the other components of the ubiquitin system have not been fully determined. In this study, we examined the following, 1), the protein profile and functional properties of LIG/HIP2, 2) the expression of LIG/HIP2 in the atherosclerotic tissue macrophages, and 3) the influence of hypoxia on poly-ubiquitination and cell death of THP-1 cell-derived macrophages. Hypoxia had no effect on LIG/HIP2 protein expression by macrophages. The LIG/HIP2 protein level in macrophages is higher than that in monocytes. Hypoxia suppressed the poly-ubiquitination and enhanced both the intracellular HIF-1α level and the cell death of macrophages.

在常氧和低氧条件下，THP-1细胞来源的单核细胞和巨噬细胞表达LIG/HIP2蛋白。由于LIG/HIP2蛋白在单核细胞中的表达受低氧上调，而低氧对单核细胞死亡的影响较小，因此LIG/HIP2对低氧诱导的单核细胞死亡可能具有保护作用。LIG/HIP2蛋白图谱以及该蛋白与泛素系统其他成分的关系尚未完全确定。在本研究中，我们研究了LIG/HIP2的蛋白谱和功能特性，2)LIG/HIP2在动脉粥样硬化组织巨噬细胞中的表达，以及3)缺氧对THP-1细胞来源的巨噬细胞多泛素化和细胞死亡的影响。低氧对巨噬细胞LIG/HIP2蛋白表达无明显影响。巨噬细胞的LIG/HIP2蛋白水平高于单核细胞。低氧抑制巨噬细胞的多泛素化，增加巨噬细胞内HIF-1α水平和细胞死亡。