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.