Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

International Journal of Molecular Sciences

Cher-Ming Liou¹  Shiow-Chwen Tsai²  Chia-Hua Kuo⁴  Hua Ting³ 

[1] Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung 402, Taiwan;Department of Sports Sciences, University of Taipei, Taipei 111, Taiwan; E-Mail:;Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; E-Mails:;Laboratory of Exercise Biochemistry, University of Taipei, Taipei 111, Taiwan; E-Mail:

关键词: heart;    apoptotic;    cocaine;    caspase;    cardiotoxicity;   

DOI  :  10.3390/ijms15045988

来源: mdpi

【 摘 要 】

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&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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland