BH4 peptide derivative from Bcl-xL attenuates ischemia/reperfusion injury thorough anti-apoptotic mechanism in rat hearts.
OBJECTIVE
To prevent apoptosis is thought to be promising for myocardial protection in cardiac surgery. Recently, we showed that BH4 domain of Bcl-xL is essential for the prevention of apoptosis, and that BH4 fused to HIV TAT protein (TAT-BH4) prevented apoptotic cell death. Then, we hypothesized TAT-BH4 may attenuate ischemia/reperfusion injury in rat hearts.


METHODS
The isolated rat hearts in the TAT-BH4 preconditioning group (BH4 group, n=8) or control group (C group, n=8) were subjected to warm ischemia (37 degrees C) for 30 min followed by 60 min of reperfusion using Langendorff perfusion system.


RESULTS
Left ventricular developed pressure and maximum dP/dt after reperfusion were significantly improved in the BH4 group than those in the C group (P<0.01). Recovery of mitochondrial respiration was significantly better in the BH4 group (P<0.05). Moreover, expression of caspase-3 and TUNEL-positive myocardium were decreased in the BH4 group than those in the C group.


CONCLUSIONS
These results demonstrated that TAT-BH4 attenuates myocardial ischemia/reperfusion injury through preventing myocardial apoptosis. Thus, TAT-BH4 may be a novel therapeutic agent for myocardial protection in cardiac surgery.
Ono
Masamichi
M
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Sawa
Yoshiki
Y
Ryugo
Masahiro
M
Alechine
Alexei N
AN
Shimizu
Shigeomi
S
Sugioka
Rie
R
Tsujimoto
Yoshihide
Y
Matsuda
Hikaru
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D017124:Conserved Sequence; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology*; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D015696:Gene Products, tat; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases