| Project/Area Number |
16500264
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KIMURA Yoshihiro Yamaguchi University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90301308)
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| Co-Investigator(Kenkyū-buntansha) |
INUI Makoto Yamaguchi University, Faculty of Medicine, Professor, 医学部, 教授 (70223237)
YAMADA Yasue Yamaguchi University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (00166737)
KO Ji-Ae Yamaguchi University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (70314797)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | sarcoplasmic reticulum / phospholamban / SERCA / oligomer / phospholipids / heart failure / 心筋小胞体 / カルシウムATPaSe / SERCA2a / ホスホランバン / 心不全 |
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| Research Abstract |
Phospholamban is a reversible inhibitor of the Ca^<2+>-ATPase of the cardiac sarcoplasmic reticulum (SR) and contributes to the regulation of heart muscle contractility. Because only the monomeric form, not the pentameric form, of phospholamban inhibits the Ca^<2+>-pumping activity of the SR, it is important to understand the dynamic equilibrium between these 2 forms.
To examine the effects of lipid environment on the SR membrane on the equilibrium between the monomeric form and the pentameric form of phospholmaban, we studied the effects of various detergents and phospholipids on the oligomeric state of phospholamban. Among the detergents examined, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) stabilized the pentameric form whereas octylglucoside was an effective inducer of dissociation into the monomer. On the basis of these properties of the 2 detergents, the effects of various phospholipids on the oligomeric state of phospholamban with the use of mixed micelles containing octylglucoside or CHAPS were examined. Among the 8 phospholipids examined, phosphatidic acid was an effective inducer of pentamer dissociation, whereas the other phospholipids exhibited pentamer-stabilizing activity. Lysophosphatidylcholine, lysophosphatidylethanolamine, and phosphatidylglycerol were highly effective stabilizers of the pentamer.
We conclude that the phospholipids in the SR membrane are important determinants of the equilibrium between the monomeric and pentameric forms of this protein. The results suggest that the metabolism of phospholipids in the cardiac SR may contribute to regulation of heart muscle contractility by shifting this equilibrium.
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