Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer's disease

Abstract

In this report, we compared total and protein-bound thiol levels in the hippocampus and cerebellum of six Alzheimer's disease (AD) patients and six age-matched control subjects. Total level of sulfhydryl (SH) groups, determined using the 5,5'-dithiobis(2-nitrobenzoic acid) method, was not significantly altered in the hippocampus and cerebellum of AD patients. The level of protein-bound SH groups, determined by labeling with 3-(N-maleimido-propionyl) biocytin, was decreased in the AD hippocampus compared with controls. Reverse transcription-polymerase chain reaction analysis of the expression of key glutathione redox system genes demonstrated the induction of glutathione reductase and glutathione peroxidase messages in the AD hippocampus. Levels of glutathione transferase mu and A4-4 messages were unchanged. This study suggests that protective antioxidant gene responses are insufficient to counteract the increased oxidative damage of proteins in a vulnerable region of the AD brain.