title: Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis.
abstract: Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) 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 methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.
authors.affiliation: Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan.
authors.forename: Cher-Ming
authors.initials: CM
authors.lastname: Liou
authors.forename: Shiow-Chwen
authors.initials: SC
authors.lastname: Tsai
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Timothy
authors.initials: T
authors.lastname: Williams
authors.forename: Hua
authors.initials: H
authors.lastname: Ting
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D005355:Fibrosis; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000697:Central Nervous System Stimulants; C491898:Fas protein, rat; D019014:fas Receptor; D008694:Methamphetamine