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 a ctivator protein-I (AP1) in the hippocampus at a dose which was ineffective in animals previously injected with vehicle alone. However, KA failed to p otentiate binding in animals injected with BSO 1 day before. The intracereb roventricular injection of BSO induced marked and prolonged depletion of a total glutathione content in murine hippocampus for 1-2 days after administ ration. These results suggest that prolonged depletion of endogenous glutat hione for a period longer than 1 day may lead to sensitization of KA signal s to potentiate AP1 DNA binding in cell nuclei and thereby modulate de novo synthesis of particular proteins at the level of gene transcription in mur ine hippocampus. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved .