Anabolic-androgenic steroids induce apoptotic cell death in adult rat ventricular myocytes.
We tested whether exposure to anabolic-androgenic steroids (AASs) would induce apoptosis in adult rat ventricular myocytes in vitro. Myocytes were exposed to stanozolol (STZ), testosterone enanthate (TE) and testosterone (T) (0.1 micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L) for 20 h. The percentage of myocytes undergoing apoptosis was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and was found to be increased when compared to control myocytes at STZ 10 micromol/L 12 +/- 2% (mean +/- SD), STZ 100 micromol/L 42 +/- 3%; TE 1 micromol/L 11 +/- 2%, TE 10 micromol/L 21 +/- 3%, TE 100 micromol/L 62 +/- 2%; T 10 micromol/L 11 +/- 2%, T 100 micromol/L 40 +/- 3% (P < 0.001 vs. CTL 2 +/- 2%). The STZ-, TE- and T-induced dose-dependent apoptotic cell death was corroborated by a significantly increased DNA laddering in myocytes exposed to STZ and T > or = 10 micromol/L and TE > or = 1 micromol/L. Notably, STZ, TE, and T exposure markedly increased the expression of the pro-apoptotic oncogene Bax-alpha, as assessed by reverse transcription-polymerase chain reaction. Taken together, these results clearly show for the first time that AASs induce apoptotic cell death in a dose-dependent manner. This finding may have important implications in understanding the pathogenesis of ventricular remodeling, cardiomyopathy, and sudden cardiac death associated with AAS abuse.
Zaugg
M
M
Department of Anesthesiology, Health Science Center at Brooklyn, State University of New York, Brooklyn, NY, USA.
Jamali
N Z
NZ
Lucchinetti
E
E
Xu
W
W
Alam
M
M
Shafiq
S A
SA
Siddiqui
M A
MA
D045930:Anabolic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology; D020287:In Situ Nick-End Labeling; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D013197:Stanozolol / Q000008:administration & dosage / Q000494:pharmacology*; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015533:Transcriptional Activation; D051028:bcl-2-Associated X Protein
D045930:Anabolic Agents; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013739:Testosterone; D013197:Stanozolol; C004648:testosterone enanthate