Methamphetamine-induced increase in striatal p53 DNA-binding activity is attenuated in Cu,Zn-superoxide dismutase transgenic mice.
The striatal DNA-binding activities of p53 as a transcription factor were gradually increased at several days after a single methamphetamine (METH) injection, while they were more rapidly increased within several hours after repeated METH injections (x4 with a 2 h interval). The elevation of striatal p53 DNA-binding after repeated METH injections was markedly attenuated in Cu,Zn-superoxide dismutase transgenic mice, but not affected by treatments with N-methyl-D-aspartate or D1 receptor antagonists. The present results suggest that METH-induced production of reactive oxygen species activates striatal p53 DNA-binding activity; this, in turn, may activate other downstream pathways that are responsible for chronic neurotoxicity of METH.
Asanuma
Masato
M
Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Okayama 700-8558, Japan. asachan@cc.okayama-u.ac.jp
Miyazaki
Ikuko
I
Higashi
Youichirou
Y
Cadet
Jean Lud
JL
Ogawa
Norio
N
D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D016166:Free Radical Scavengers; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D000697:Central Nervous System Stimulants; D016166:Free Radical Scavengers; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D016159:Tumor Suppressor Protein p53; D008694:Methamphetamine; D013482:Superoxide Dismutase