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

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: JICHI MEDICAL SCHOOL
• Principal Investigator: YAMADA Shigeki JMS, School of Medicine, Assistant Professor, 医学部, 講師 (80220375)
• Co-Investigator(Kenkyū-buntansha): KANNO Hiroshi Yokohama City University, School of Medicine, Associate Professor, 医学部, 助教授 (40244496)
• Project Period (FY): 2003 – 2005
• Keywords: LIG / HIP2 / ubiquitination / atherosclerosis / monocytes / macrophages / apoptosis / TP-1 cells

Research Abstract

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.