2003 Fiscal Year Final Research Report Summary
Study on cardiac dysfunction caused by abnormal ionic regulation.
| Project/Area Number |
14370236
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Senri-Kinran University (2003)
National Cardiovascular Center Research Institute (2002) |
|---|
Principal Investigator |
SHIGEKAWA Munekazu Senri-Kinran University, Dept.of Human Life Sciences, Professor, 生活科学部, 教授 (00113738)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IWATA Yuko National Cardiovascular Center, Dept.of Molecular Physiology, Researcher, 循環分子生理部, 室員 (80171908)
DOI Junko Senri-Kinran University, Dept.of Human Life Sciences, Assistant Professor, 生活科学部, 講師 (50343728)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Keywords | Dilated Cardiomyopathy / Muscular Dystrophy / Dystrophin-glycoprotein Complex / Muscle degeneration / Na+ / Ca2+ Exchanger / Na+ / H+ Exchanger |
|---|
| Research Abstract |
Disruption of the dystrophin-glycoprotein complex(DGC) caused by genetic defects of dystrophin or sarcoglycans results in muscular dystrophy and/or cardiomyopathy in humans and animal models. However, the key early molecular events leading to myocyte degeneration remain elusive. In this study, we observed that the growth factor-regulated cation channel GRC, which belongs to the transient-receptor-potential(TRP) channel family, is elevated in the sarcolemma of skeletal and/or cardiac muscle in dystrophic human patients and animal models deficient in dystrophin or 5-sarcoglycan. However, total cell GRC does not differ markedly between normal and dystrophic muscles. Analysis of the properties of myotubes prepared from δ-sarcoglycan-deficient BIO14.6 hamsters revealed that GRC is activated in response to myocyte stretch and is responsible for enhanced Ca^<2+> influx and resultant cell damage as measured by creatine phosphokinase efflux. We found that cell stretch increases GRC translocation to the sarcolemma, which requires entry of external Ca^<2+>. Consistent with these findings, cardiac-specific expression of GRC in a transgenic mouse model produced cardiomyopathy due to Ca^<2+> overloading, with disease expression roughly parallel to sarcolemmal GRC levels. The results suggest that GRC is a key player in the pathogenesis of myocyte degeneration caused by DGC disruption. Besides these studies, we explored the regulatory mechanisms of Na^+/Ca^<2+> and Na^+/H^+ exchangers and their roles in the genesis of cardiac dysfunction.
|
Research Products
(16 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Publications] Wakabayashi, S., Pang, T., Hisamitsu, T., Shigekawa, M.: "Two Fundamental Regulatory Factors of the Na^+/H^+ Exchangers : The Proton and CHP.(The Sodium-Hydrogen Exchange. From Molecule to its Role in Disease.(Ed. by Karmazyn, M., Avkiran, M., Fliegel, L.))"Kluwer Academic Publishers. 35-49 (2003)
Description
「研究成果報告書概要(欧文)」より
