2011 Fiscal Year Final Research Report
Development of new therapeutic strategy for rescuing cardiomyopathy via inhibition of protein aggregation
| Project/Area Number |
21590299
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Iwate Medical University (2011)
National Research Institute for Child Health and Development (2009-2010) |
|---|
Principal Investigator |
SANBE Atsushi 岩手医科大学, 薬学部, 教授 (30425706)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Keywords | 循環 |
|---|
| Research Abstract |
A missense mutation in crystallin, alpha B(CryAB) causes desmin-related cardiomyopathy, which is characterized by the formation of aggresomes containing CryAB. Cardiac disease in desmin-related cardiomyopathy can be recapitulated in transgenic(TG) mice by expressing the mutant CryAB protein specifically in the cardiomyocytes, which causes perinuclear formation of aggresomes. To analyze the role of HDAC6 in cardiac disease in desmin-related cardiomyopathy, cardiac-specific TG mice with overexpressed dominant negative HDAC6 or wild-type HDAC6 were generated. The mice with dominant negative HDAC6 showed increased acetylated tubulin levels concomitantly with higher numbers of CryAB-positive aggresomes and enhancement of heart weight/body weight ratio, while overexpression of wild-type HDAC6 was protective in the mutant CryAB TG mice hearts. These results indicate that HDAC6 inhibition exacerbates cardiac disease in mice with desmin-related cardiomyopathy.
|
