Methamphetamine-induced apoptosis in a CNS-derived catecholaminergic cell line.
Methamphetamine (METH) causes neurotoxic damages to the dopaminergic system in mammals, but whether it exerts toxicity to dopamine cells in culture has not been fully explored. In order to develop an in vitro model of METH-induced dopamine neurotoxicity toward more systemical examination of the mechanism, we investigated METH toxicity in a clonal dopamine producing cell line (CATH.a). We show in the present study that METH produces a time- and dose-dependent increase in cell death via a process similar to apoptosis. The METH toxicity seems to be produced by oxidative stress, as it was attenuated by the antioxidant glutathione, and to involve dopamine because dopamine release and synthesis inhibitors attenuated the toxicity. This catecholaminergic cell line derived from the central nervous system may become a useful in vitro model to elucidate the mechanism underlying the METH-induced dopaminergic neuronal damage.
Choi
Hyun Jin
HJ
Department of Biochemistry, University of Ulsan College of Medicine, Seoul, Korea.
Yoo
Tae Moo
TM
Chung
Soo Youn
SY
Yang
Ji Sun
JS
Kim
Joo-Il
JI
Ha
Eun Sook
ES
Hwang
Onyou
O
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D044005:Tetrahydroisoquinolines; D013997:Time Factors
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D011500:Protein Synthesis Inhibitors; D044005:Tetrahydroisoquinolines; D003609:Dactinomycin; D008694:Methamphetamine; C074266:4-phenyl-1,2,3,4-tetrahydroisoquinoline; D003513:Cycloheximide; D005978:Glutathione; D004298:Dopamine