| Project/Area Number |
21590651
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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 |
Hygiene
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| Research Institution | University of Toyama |
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Principal Investigator |
INADERA Hidekuni 富山大学, 大学院・医学薬学研究部(医学), 教授 (10301144)
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| Research Collaborator |
CUI Zheng-guo 富山大学, 大学院・医学薬学研究部(医学), 助教 (90572115)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 環境保健 / カドミウム / アポトーシス / 化学物質 |
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| Research Abstract |
Cadmium(Cd) is a potential environmental hazard that induces disorders in various organs. In this study, we examined the molecular mechanisms involved in the adaptive response to Cd-induced apoptosis in human myelomonocytic lymphoma U937 cells. When U937 cells were treated with 50μM cadmium chloride(CdCl2) for 12 hours, significant apoptosis occurred. This was associated with an increase in intracellular reactive oxygen species(ROS), sustained phosphorylation of JNK, activation of caspase-3, a decrease in Mcl-1(anti-apoptotic Bcl-2 proteins), and increases in Bim, Noxa and tBid(a pro-apoptotic protein under the Bcl-2 family). No apoptosis occurred when the cells were treated with 1μM CdCl2 for 72 hours. However, pretreatment with low-dose CdCl2 dramatically altered the sensitivity of the cells to 50μM CdCl2 with inhibition of apoptosis. Concomitantly, there were significant decreases in the generation of intracellular ROS and the activation of JNK. Pretreatment with 1μM CdCl2 also attenuated the decrease in Mcl-1 and the increases in Bim, Noxa and tBid induced by 50μM CdCl2. The inhibition of apoptosis following exposure to low-dose Cd suggests a potential mechanism that may help explain why people exposed to low doses of Cd for a long time have an increased risk of developing certain cancers.
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