Dystrophin upregulation in pressure-overloaded cardiac hypertrophy in rats.
Dystrophin is a cytoskeletal protein localized to the sarcolemma of skeletal and cardiac muscle, and neurons. We have recently demonstrated that a significant cardiac damage including myocytes injury, inflammation, and fibrosis, was found in dystrophin-deficient myocardium during pressure overload [Kamogawa et al., 2001: Cardiovasc Res 50:509-515]. However, little is known about how the cardiac sarcolemmal cytoskeleton produces qualitative and quantitative changes in response to pressure overload. Accordingly, we investigated dystrophin gene expression and protein accumulation during cardiac hypertrophy. Cardiac hypertrophy was produced by banding of the abdominal aorta of rats. Total RNA from the left ventricle of the heart was used for a quantitative reverse transcription-polymerase chain reaction (RT-PCR). Dystrophin mRNA expression significantly increased by 33 +/- 18% at 1 day (P < 0.05) and 45 +/- 19% at 2 days (P < 0.01) after banding, while G3PDH mRNA showed no significant change. RT-PCR for dystrophin tissue-specific exon 1 revealed that only muscle type promoter, but not non-muscle type promoter (brain and Purkinje-cell type), was activated immediately after banding. Immunohistochemistry for dystrophin showed intense cellular membrane staining with an increase in the perimeter of the myocytes by 14% at 3 days (46.3 microm, P < 0.01) and 19% at 7 days (51.2 microm, P < 0.01) after banding. Western blotting also showed dystrophin protein increased by 14 +/- 6% at 2 days (P < 0.05) and by 32 +/- 10% at 3 days (P < 0.01) after aortic banding. In conclusion, upregulation of dystrophin mRNA expression and protein accumulation occurs in response to cardiac hypertrophy. These data and the vulnerability of dystrophin-deficient myocardium to pressure overload suggest that dystrophin could play an important role in maintaining the integrity of the sarcolemma.
Maeda
Masato
M
The First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakura-gaoka, Kagoshima 890-8520, Japan.
Biro
Sadatoshi
S
Kamogawa
Yasuyuki
Y
Hirakawa
Tatsumi
T
Setoguchi
Manabu
M
Tei
Chuwa
C
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D048429:Cell Size / Q000235:genetics; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics*
D016189:Dystrophin; D012333:RNA, Messenger; D005993:Glycerolphosphate Dehydrogenase; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+)