Life-and-death decisions of myoblast cells during differentiation
| Project/Area Number |
18570190
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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 |
Cell biology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
MORISHIMA Nobuhiro The Institute of Physical and Chemical Research, Molecular Membrane Biology Laboratory, Senior Research Scientist (40182232)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | myogenesis / apoptosis / cell culture / endoplasmic reticulum stress / caspase |
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| Research Abstract |
Endoplasmic reticulum (ER) stress is caused by the accumulation of unfolded proteins in the ER, which occurs under a variety of conditions. We recently demonstrated that ER stress signaling occurs during myoblast differentiation in vivo. This signaling results in apoptosis in a subpopulation of myoblasts. To further examine the role of ER stress during myogenesis, we exposed cultured myoblasts to ER stress inducers during the transition from proliferation to differentiation. Increased ER stress enhanced differentiation-associated apoptosis of myoblasts. We found that the surviving myoblast cells efficiently differentiated into contracting myofibers that are rarely found in culture. Our observations suggest that ER stress exerts a positive effect on myofiber formation, possibly mimicking the action of signals that drive apoptosis and differentiation in vivo. Previous studies have revealed that insulin-like growth factor II (IGF-II) secreted in the medium regulates myoblast differentiati
… More
on. We found that levels of extracellular IGF-II after pretreatment with ER stress inducers were lower than those IGF-II secreted from differentiating myoblasts without pretreatment. The lower levels of IGF-II is at least partly due to a decrease in its synthesis. Addition of recombinant IGF-II to the medium nearly completely prevented apoptosis of differentiating myoblasts with or without pretreatment. The level of extracellular IGF-II can be modulated as a result of its internalization by the IGF-II/mannose-6-phosphate (Man-6-P) receptor. Extracellular Man-6-P-modified procathepsin B decreased after pretreatment that may facilitate the association of IGF-II and its receptor. These results suggest that pretreatment of myoblasts with ER stress inducers reduces IGF-II synthesis and enhances internalization of extracellular IGF-II by the IGF-II/Man-6-P receptor. We also found that the level of Bc1-xL in apoptotic cells was lower than that in proliferating cells and surviving cells. This result suggests that negative selection, based on Bcl-xL level, operates specifically during myoblast differentiation. Less
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Report
(3 results)
Research Products
(23 results)
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[Presentation] 小胞体ストレスと筋分化2007
Author(s)
森島 信裕
Organizer
解剖学会全国学術大会シンポジウム
Place of Presentation
大阪国際会議場、大阪
Year and Date
2007-03-28
Description
「研究成果報告書概要(和文)」より
Related Report
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