Sensitization by prolonged glutathione depletion of kainic acid to potentiate DNA binding of the nuclear transcription factor activator protein-1 in murine hippocampus.
In four of four mice intracerebroventricularly injected with the inhibitor of glutathione synthesis L-buthionine-[S,R]-sulfoximine (BSO) 2 days before, an intraperitoneal injection of kainic acid (KA) invariably led to marked potentiation of DNA binding activity of the nuclear transcription factor activator protein-I (AP1) in the hippocampus at a dose which was ineffective in animals previously injected with vehicle alone. However, KA failed to potentiate binding in animals injected with BSO 1 day before. The intracerebroventricular injection of BSO induced marked and prolonged depletion of a total glutathione content in murine hippocampus for 1-2 days after administration. These results suggest that prolonged depletion of endogenous glutathione for a period longer than 1 day may lead to sensitization of KA signals to potentiate AP1 DNA binding in cell nuclei and thereby modulate de novo synthesis of particular proteins at the level of gene transcription in murine hippocampus.
Kitayama
T
T
Department of Pharmacology, Setsunan University, Hirakata, Osaka, Japan.
Ogita
K
K
Nomoto
M
M
Yoneda
Y
Y
D000818:Animals; D001483:Base Sequence; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1; D019328:Buthionine Sulfoximine; D004247:DNA; D005978:Glutathione; D007608:Kainic Acid