1996 Fiscal Year Final Research Report Summary
The pathophysiological role of calsequestrin for the development of cardiac hypertrophy
| Project/Area Number |
07670754
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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 |
Circulatory organs internal medicine
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| Research Institution | Gunma University |
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Principal Investigator |
ARAI Masashi Gunma University, 2nd Dept of Int.Med, Research & Clinical Fellow, 医学部, 助手 (60270857)
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| Project Period (FY) |
1995 – 1996
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| Keywords | calsequestrin / calcium / sarcoplasmic reticulum / cardiac hypertrophy / sodium / proton antiporter / transgenic mice / calcium pump |
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| Research Abstract |
The purpose of this study was to clarify the role of calsequestrin, the major Ca2+ binding protein located in the sarcoplasmic reticulum, for the development of cardiac hypertrophy. We measured the Ca2+ storage capacity of calsequestrin arid the Ca2+ uptake capacity of sarcoplasmic reticulum Ca2+-ATPase using transgenic mice that overexpress sodium/proton antiporter gene as a model of cardiac hypertrophy. These mice develop hypertension and subsequent cardiac hypertrophy under high salt loading condition. Our experimental results suggest that :
1) Ca2+ storage capacity as well as Ca2+ uptake function is the important determinant of cardiac mechanical properties. Both functions are diminished in hypertrophied hearts, which will significantly contribute the decreased heart rate and slowed relaxation and contraction observed in hemodynamically overloaded hearts.
2) Although the Ca2+ storage function of calsequestrin was decreased in hypertrophied hearts, the expression level of calsequestrin mRNA remained unaltered. Translational modification of calsequestrin gene may explain the discrepancy between the function and the mRNA expression level.
3) It has been known that Ca2+ is a second messenger which induces cellular proliferation and gene transcription. The Ca2+ uptake and storage capacity was diminished in the examined hearts. Therefore, the Ca2+ transported by calsequestrin and Ca2+-ATPase may not function as a cellular hypertrophic signal, but merely as a regulator of cardiac function.
Recently, it was reported that calsequestrin contacts with ryanodine receptor, the major Ca2+ release channel of sarcoplasmic reticulum. Future studies should be aimed to measure calcium release activity simultaneously and clarify whether calsequestrin has a regulatory function for Ca2+ release. In addition, the transcriptional and translational regulation of calsequestrin gene should also be determined.
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