LDL-dependent cytotoxicity of Shiga toxin in the cells devoid of Gb3
Project/Area Number |
23590515
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Bacteriology (including Mycology)
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Research Institution | Nara Medical University |
Principal Investigator |
KITA eiji 奈良県立医科大学, 医学部, 教授 (90133199)
|
Co-Investigator(Kenkyū-buntansha) |
MIZUNO Fumiko 奈良県立医科大学, 細菌学, 講師 (70271202)
SAGESHIMA Noriko 奈良県立医科大学, 細菌学, 助授 (30398432)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | 志賀毒素 / 腸管感染症 / HUS / 腸管出血性大腸菌 / 中性糖セラミド / リポ蛋白 |
Research Abstract |
The present investigation was aimed to clarify the mechanism by which Shiga toxin (Stx) would express its biological action in the cells devoid of Gb3. Monohexosylceramide (Lc2Cer), Gb3Cer, and Gb4Cer were found in both intestinal and plasma glycosphingolipid (GSL). Plasma GSLs exhibited heterogeneity of free fatty acids in their lipid ceramide anchors. Synthesized GSL-Stx2 liposome bound to LDL and VLDL with high affinity. GSL-Stx2 liposomes with the high affinity have the relative composition of C24:0/C24:1 as Gb3Cer moiety, accounting for their heterogeneity. GSL-Stx2 liposomes capable of binding to LDL were easily taken-up by the cells devoid of Gb3 receptors. These results indicated a new mechanism of the expression of Stx cytotoxicity to the cells, devoid of Gb3 receptors: the complex of GSL-Stx-LDL can be taken-up through LDL receptors before internalization.
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Report
(4 results)
Research Products
(15 results)