Methamphetamine activates DNA binding of specific redox-responsive transcription factors in mouse brain.
Cellular oxidative stress and alterations in redox status can be implicated in methamphetamine (METH)-induced neurotoxicity. To elucidate the molecular signaling pathways of METH-induced neurotoxicity, we investigated the effects of a single intraperitoneal injection of METH (1.0, 10, or 20 mg/kg) on DNA-binding activity of specific redox-sensitive transcription factors in mouse brain. Transcription factors studied included activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), cAMP-responsive element-binding protein (CREB), SP-1, and signal transducers and activators of transcription (STAT1 and STAT3). Significant and dose-dependent inductions of AP-1 and CREB DNA-binding activities were observed in four different regions (striatum, frontal cortex, hippocampus, and cerebellum) isolated from the brains of mice injected with METH. However, injections with METH did not affect DNA binding activities of NF-kappaB, SP-1, STAT1, and STAT3. These results suggest that METH-induced oxidative stress may trigger the molecular signaling pathways via specific and selective activation of AP-1 and CREB.
Lee
Yong Woo
YW
Division of Neurosurgery, Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
Son
Kwang Won
KW
Flora
Govinder
G
Hennig
Bernhard
B
Nath
Avindra
A
Toborek
Michal
M
D051697:Activating Transcription Factor 1; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010759:Phosphorus Isotopes; D011033:Podophyllin / Q000031:analogs & derivatives* / Q000378:metabolism; D011034:Podophyllotoxin / Q000031:analogs & derivatives; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D004268:DNA-Binding Proteins; D018765:Dopamine Uptake Inhibitors; D016328:NF-kappa B; D010759:Phosphorus Isotopes; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D008694:Methamphetamine; C003170:mitopodozide; D011033:Podophyllin; D011034:Podophyllotoxin