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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 (CC BY 3.0).
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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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