Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway.
Methamphetamine is a neurotoxic drug of abuse known to cause cell death both in vitro and in vivo. Nevertheless, the molecular and cellular mechanisms involved in this process remain to be clarified. Herein, we show that methamphetamine-induced apoptosis is associated with early (2 h) overexpression of bax, decreases of mitochondrial membrane potential and oxygen consumption as well as release of cytochrome c from mitochondria. In addition, activated caspase-9 was detected at 4 h post-METH exposure. Cell death was detectable by annexin V and propidium iodide staining after 8 h of methamphetamine exposure. At that time, the majority of the cells were stained by annexin V alone, with some cells being stained for both annexin V and propidium iodide. Moreover, cleavage of caspase-3, poly (ADP-ribose) polymerase and DNA fragmentation-related factor 45 was detected at 8 h post drug treatment. These results indicate that methamphetamine-induced apoptotic cell death results from early overexpression of bax, reduction of mitochondrial respiration and membrane potential and release of mitochondrial cytochrome c with subsequent activation of the caspase cascade.
Deng
Xiaolin
X
Molecular Neuropsychiatry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Cai
Ning-Sheng
NS
McCoy
Michael T
MT
Chen
Weiguo
W
Trush
Michael A
MA
Cadet
Jean Lud
JL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine