(Circulation. 2000;102:344.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
ß-Adrenergic Receptor Subtypes Differentially Affect Apoptosis in Adult Rat Ventricular Myocytes
From the Department of Anesthesiology (M.Z.), Department of Neurology (W.X., S.A.S.), and Department of Anatomy and Cell Biology and Center for Cardiovascular and Muscle Research (N.Z.J., M.A.Q.S.), Health Science Center at Brooklyn, State University of New York, and the Laboratory for Soft Tissue Research, Hospital for Special Surgery (E.L.), New York, NY.
Correspondence to Dr M.A.Q. Siddiqui, Professor and Chairman, Department of Anatomy and Cell Biology, State University of New York, 450 Clarkson Ave, Box 5, Brooklyn, NY 11203. E-mail msiddiqui{at}netmail.hscbklyn.edu
Background—Catecholamine-induced apoptosis is mediated by activation of the ß-adrenergic signaling pathway. We tested the hypothesis that ß1- and ß2-adrenergic receptor (AR) subtypes differentially affect apoptosis in adult rat ventricular myocytes in vitro.
Methods and Results—Myocytes were first exposed to
norepinephrine (NE) alone (10 µmol/L) or NE+atenolol
(AT) (10 µmol/L) for 12 hours. AT, a ß1-selective
AR antagonist, abolished the NE-induced increase in nick
end-labeling (TUNEL)–positive cells compared with control (NE, 33±3%
versus control, 3±1%, P<0.0001; NE+AT, 4±2% versus
control, 3±1%, P=0.98). Annexin V staining, DNA
laddering, and caspase activity determinations corroborated these
results. Subsequent experiments under prazosin treatment established
the apoptosis dose-response curves for the increasingly
ß2-selective AR agonists isoproterenol (ISO)
(ß1
ß2) and albuterol (ALB)
(ß2>ß1). ISO and ALB induced significantly
less apoptosis than NE (ß1>ß2) at
equimolar concentrations as assessed by TUNEL staining [1
µmol/L: NE (8±2%)ISO (7±1%)>ALB (2±1%); 10 µmol/L:
NE (35±2%)>ISO (23±1%)>ALB (3±1%); 100 µmol/L: NE
(50±2%)>ISO (29±2%)>ALB (14±1%), P<0.0001
except for NE versus ISO at 1 µmol/L with
P=0.62]. ALB-induced apoptosis at 100
µmol/L was abolished by AT (10 µmol/L), indicating a
ß1AR-mediated effect. Importantly, ICI 118551
(0.1 µmol/L), a highly selective ß2AR
antagonist, did not decrease the percentage of NE-, ISO-,
and ALB-induced apoptosis. Reverse transcription–polymerase
chain reaction studies revealed that AT completely reversed the
ß-adrenergic signaling–induced changes in the Bcl-2–to-Bax
ratio.
Conclusions—These observations provide evidence that ßAR-mediated apoptotic death signaling is largely dissociated from ß2ARs and selectively mediated by ß1ARs in adult rat ventricular myocytes.
Key Words: receptors, adrenergic, beta • catecholamines • apoptosis • heart failure
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|
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|
|
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|
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|
|
|
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|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|