| Project/Area Number |
15510055
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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 |
Risk sciences of radiation/Chemicals
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| Research Institution | Nagasaki University |
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Principal Investigator |
URATA Yoshishige Nagasaki University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (30185087)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Shinzi Nagasaki University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (50186889)
IHARA Yoshito Nagasaki University, Graduate School of Biomedical Sciences, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (70263241)
KONDO Takahito Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00158908)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | γ-GCS / GST / Akt / p53 |
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| Research Abstract |
Oxidized low-density lipoprotein (oxLDL) modifies macrophage inflammatory responses in the pathogenesis of atherosclerosis. In the present study, we focused on gamma-glutamylcysteine synthetase (gamma-GCS), a rate limiting enzyme of glutathione synthesis, and examined whether inflammatory stimulation of gamma-GCS gene in macrophages by lipopolysaccharide(LPS) is modified when the cells were exposed to oxLDL. We found that the nuclear factor-kappa B(NF-kappa B)-mediated induction of gamma-GCS by LPS (100 ng/ml) was suppressed by a 48-h pre-treatment with oxLDL (50 micro/ml), and this was due to a decrease in the DNA-binding activity of NF-kappa B. Furthermore, pre-treatment with oxLDL caused a carbonylation of NF-kappa B subunit p65. With alpha-tocopherol, the oxLDL-induced carbonylation of proteins decreased with a restoration of DNA-binding activity of NF-kappa B. Together, these indicate that oxidative modification of NF-kappa B suppresses LPS-induced expression of gamma-GCS gene in ox-LDL-treated cells, suggesting an implication of oxLDL-induced modulation of NF-kappa B signaling with atherosclerosis.
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