Effects of glutathione depletion by 2-cyclohexen-1-one on excitatory amino acids-induced enhancement of activator protein-1 DNA binding in murine hippocampus.
We have investigated the role of glutathione in mechanisms associated with excitatory amino acid signaling to the nuclear transcription factor activator protein-1 (AP1) in the brain using mice depleted of endogenous glutathione by prior treatment with 2-cyclohexen-1-one (CHX). In the hippocampus of animals treated with CHX 2 h before, a significant increase was seen in enhancement of AP1 DNA binding when determined 2 h after the injection of kainic acid (KA) at low doses. The sensitization to KA was not seen in animals injected with CHX 24 h before, in coincidence with the recovery of glutathione contents to the normal levels. By contrast, CHX did not significantly affect the potentiation by NMDA of AP1 binding under any experimental conditions. Prior treatment with CHX resulted in facilitation of behavioral changes induced by KA without affecting those induced by NMDA. These results suggest that endogenous glutathione may be at least in part involved in molecular mechanisms underlying transcriptional control by KA, but not by NMDA, signals of cellular functions.
Department of Pharmacology, Setsunan University, Hirakata, Osaka, Japan. ogita@pharm.setsunan.ac.jp
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D000818:Animals; D001665:Binding Sites; D003512:Cyclohexanones / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011187:Posture; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014202:Tremor / Q000139:chemically induced / Q000503:physiopathology
D003512:Cyclohexanones; D018846:Excitatory Amino Acids; D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1; C028215:2-cyclohexen-1-one; D016202:N-Methylaspartate; D005978:Glutathione; D007608:Kainic Acid