| Project/Area Number |
19590289
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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 |
General medical chemistry
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
MANNO Sumie Tokyo Women's Medical University, 医学部, 講師 (10101205)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAKUWA Yuichi 東京女子医科大学, 医学部, 教授 (40113740)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 赤血球 / スペクトリン / 変形能(膜伸展性) / 糖化 / リボース / ペントシジン / 寿命 / ATP |
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| Research Abstract |
Human erythrocytes are continuously exposed to glucose which reacts with the amino terminus of the ・-chain of hemoglobin (Hb) to form glycated Hb, HbA1c, levels of which increase with the age of the circulating cell. In contrast to extensive insights into glycation of hemoglobin, little is known about glycation of erythrocyte membrane proteins. In the present study, we explored the conditions under which glucose and ribose can glycate spectrin, both on the intact membrane and in solution and the functional consequences of spectrin glycation. While purified spectrin could be readily glycated, membrane-associated spectrin could be glycated only after ATP depletion and consequent translocation of phosphatidylserine (PS) from the inner to the outer lipid monolayer. Glycation of membrane-associated spectrin led to a marked decrease in membrane deformability. We further observed that only PS-binding spectrin repeats are glycated. We infer that the absence of glycation in situ is the consequence of the interaction of the target lysine and arginine residues with PS and thus being inaccessible for glycation. The reduced membrane deformability following glycation in the absence of ATP is likely the result of the inability of the glycated spectrin repeats to undergo the obligatory unfolding as a consequence of inter-helix crosslinks. We thus postulate that erythrocytes through the use of an ATP-driven phospholipids translocase have evolved a protective mechanism against spectrin glycation and thus maintain their optimal membrane function during their long circulatory life span.
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