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Int. J. Mol. Sci. 2014, 15(4), 5988-6001; doi:10.3390/ijms15045988
Article

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

1,2
,
3
,
4
,
2,5,†
 and
6,7,8,†,*
1 Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung 402, Taiwan 2 Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan 3 Department of Sports Sciences, University of Taipei, Taipei 111, Taiwan 4 Laboratory of Exercise Biochemistry, University of Taipei, Taipei 111, Taiwan 5 Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung 402, Taiwan 6 Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 402, Taiwan 7 Department of Healthcare Administration, Asia University, Taichung 413, Taiwan 8 School of Rehabilitation Medicine, Shanghai University of TCM, Shanghai 201203, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 12 November 2013 / Revised: 5 March 2014 / Accepted: 24 March 2014 / Published: 9 April 2014
(This article belongs to the collection Programmed Cell Death and Apoptosis)
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Abstract

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.
Keywords: heart; apoptotic; cocaine; caspase; cardiotoxicity heart; apoptotic; cocaine; caspase; cardiotoxicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Liou, C.-M.; Tsai, S.-C.; Kuo, C.-H.; Ting, H.; Lee, S.-D. Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse. Int. J. Mol. Sci. 2014, 15, 5988-6001.

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