Cardiac Fas-dependent and mitochondria-dependent apoptosis after chronic cocaine abuse.
To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&amp;E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse.
Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung 402, Taiwan. liouk04.peter@msa.hinet.net.
Cher-Ming
CM
Liou
Department of Sports Sciences, University of Taipei, Taipei 111, Taiwan. sctsai6@gmail.com.
Shiow-Chwen
SC
Tsai
Laboratory of Exercise Biochemistry, University of Taipei, Taipei 111, Taiwan. kuochiahua@gmail.com.
Chia-Hua
CH
Kuo
Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan. huating@csmu.edu.tw.
Hua
H
Ting
Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 402, Taiwan. shinda@mail.cmu.edu.tw.
Shin-Da
SD
Lee
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002908:Chronic Disease; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D059467:Transcriptome; D019014:fas Receptor / Q000378:metabolism*
D019014:fas Receptor; D003042:Cocaine