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Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway.
- Source :
-
Neuropharmacology [Neuropharmacology] 2002 May; Vol. 42 (6), pp. 837-45. - Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- Animals
Apoptosis physiology
Cell Death drug effects
Cell Death physiology
Cell Line, Transformed enzymology
Corpus Striatum enzymology
Dopamine Uptake Inhibitors pharmacology
Mitochondria enzymology
Rats
Signal Transduction physiology
Apoptosis drug effects
Cell Line, Transformed cytology
Cell Line, Transformed drug effects
Corpus Striatum cytology
Corpus Striatum drug effects
Methamphetamine pharmacology
Mitochondria drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0028-3908
- Volume :
- 42
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12015210
- Full Text :
- https://doi.org/10.1016/s0028-3908(02)00034-5