Direct interactions of methamphetamine with the nucleus.
Possible direct effects of methamphetamine (METH) on transcription factors AP-1 and cAMP response element-binding protein (CREB) in the nucleus were assessed by electrophoretic mobility-shift assay. In vitro addition of METH to nuclear extract from brain tissue increased DNA-binding activities of both transcription factors. In addition, injections of METH to mice induced increases in the binding of AP-1 and CREB, which were depleted by preincubating the nuclear extract with anti-METH antibody. We also examined the cellular distribution of METH in mesencephalic neuronal cells using an immunofluorescence experiment with anti-METH antibody. METH-like immunoreactivity was seen to accumulate in the cytosol 4-6 h after the METH treatment. Furthermore, METH-positive signals were also observed in the nuclei of the METH-treated cells. The present study is the first demonstration that METH can have direct effects on DNA-binding protein complex by redistributing not only in the cytosol but also into the nucleus.
Asanuma
M
M
Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, MD, USA. asachan@cc.okayama-u.ac.jp
Hayashi
T
T
Ordonèz
S V
SV
Ogawa
N
N
Cadet
J L
JL
D000818:Animals; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D018808:Transcription Factor AP-1; D008694:Methamphetamine