AP-1 DNA-binding activation by methamphetamine involves oxidative stress.
Methamphetamine (METH) caused dose-dependent increases in AP-1 DNA-binding activity in both nontransgenic (Non-Tg) and CuZn-SOD transgenic (SOD-Tg) mice. However, the increases in SOD-Tg mice were less prominent than those observed in Non-Tg animals. The time-course of METH-induced AP-1 changes was similar in both strains of mice. AP-1 binding activity showed an initial increase at 1 h, peaked at 3 h, and then gradually declined. AP-1 binding activity was back to normal by the 72-h time point. Regional analyses of METH effects revealed increases in the caudate putamen and cerebellum, with the striatum showing relatively higher METH-induced AP-1 DNA-binding activation. These regional effects were also attenuated in the SOD-Tg mice. These data indicate that METH-induced stimulation of AP-1 DNA-binding depends on cellular redox status. These results are consistent with in vitro studies that have reported that several transcription factors are regulated through redox mechanisms.
Sheng
P
P
Section of Molecular Neuropsychiatry, Intramural Research Program, NIH/NIDA, Baltimore, Maryland 21224, USA.
Wang
X B
XB
Ladenheim
B
B
Epstein
C
C
Cadet
J L
JL
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D018808:Transcription Factor AP-1; D008694:Methamphetamine; D004247:DNA; D013482:Superoxide Dismutase