| Project/Area Number |
16591890
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Nagasaki university |
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Principal Investigator |
TASHIRO Shigeki Nagasaki University, Graduate School of Biomedical Sciences, Instructor, 大学院・医歯薬学総合研究科, 助手 (20300882)
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| Co-Investigator(Kenkyū-buntansha) |
HOTOKEZAKA Yuka Nagasaki University, Hospital of Medicine and Dentistry, Instructor, 医学部・歯学部附属病院, 助手 (10244089)
KATAYAMA Ikuo Nagasaki University, Hospital of Medicine and Dentistry, Instructor, 医学部・歯学部附属病院, 助手 (80295089)
SUMI Tadateru Nagasaki University, Graduate School of Biomedical Sciences, Instructor, 大学院・医歯薬学総合研究科, 助手 (80284701)
NAKAMURA Takashi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30172406)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | acetylation / cPLA2 / DNA damage / Tip60 / UV |
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| Research Abstract |
Cytosolic phospholipase A_2 (cPLA_2) cleaves menbrane phospholipids to release arachidonic acid, and participates in allergic responses, fertility, and cell growth regulation after DNA damage, implying versatile roles of the protein in the cell. Here we show that cPLA_2 regulates heat-shock responses of the cell. The inhibition of cell growth in response to heat stress was correlated with the cPLA_2 expression levels of various cell lines as well as with the cPLA_2 expression levels at different cell densities. Lung fibroblasts isolated from cPLA_2^<-/-> mice were more resistant to heat-shock than cells from cPLA_2^<+/+> mice. Overexpression of cPLA_2 renders the cells heat-prone, an effect that is lost or greatly diminished when the cells were cotransfected with the cPLA_2 protein lacking one of the functional domains, such as the phosphorylation site (Ser 505) or N-terninal CaLB domain. Heat stress caused DNA double strand breaks as evidenced by H2AX nuclear foci formation. Furthermore, the nuclear levels of cPLA_2 were correlated with the magnitude of H2AX foci formation in response to heat shock. Following heat-shock, cPLA_2 translocates preferentially to the nucleus and then binds with acetyltransferase Tip60. The role of Tip60 in heat-shock responses in the cells was suggested by the findings that Tip60 upregulation increased the heat sensitivity and H2AX nuclear foci formation, and Tip60 downregulation decreased them. Taken together, these results suggest a critical role of cPLA_2 in heat-shock responses in mammalian cells.
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