Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol.
Sarcolemma integrity is stabilized by the dystrophin-associated glycoprotein complex that connects actin and laminin-2 in contractile machinery and the extracellular matrix, respectively. Interruption of the connection by the primary gene defect or acquired pathological burden can cause cardiac failure. The purposes of the present study were to verify whether dystrophin is disrupted in acute myocardial injury after the isoproterenol overload (10 mg/kg) and to examine its relation to myocardial cell apoptosis in rats. This injury from 4-16 h at the subendocardium was accompanied by dystrophin disruption and dislocation from subsarcolemma to cytoplasm, which were confirmed by immunohistology and Western blotting. However, delta-sarcoglycan was thoroughly preserved in sarcolemma. The dystrophin degradation preceded the appearance of apoptotic cells and exactly coincided with the transferase-mediated dUTP-biotin nick end labeling-positive cardiomyocytes (TUNEL), as was verified by double-staining. These data suggest that beta-adrenergic stimulation induces dystrophin breakdown followed by apoptosis.
Xi
H
H
Department of Internal Medicine, Tokyo University Hospital, University of Tokyo, Japan.
Shin
W S
WS
Suzuki
J
J
Nakajima
T
T
Kawada
T
T
Uehara
Y
Y
Nakazawa
M
M
Toyo-oka
T
T
D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000032:analysis; D049030:Dystroglycans; D016189:Dystrophin / Q000032:analysis / Q000502:physiology*; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049030:Dystroglycans; D007545:Isoproterenol