Gender differences in glutathione metabolism in Alzheimer's disease.
The mechanism underlying Alzheimer's disease (AD), an age-related neurodegenerative disease, is still an area of significant controversy. Oxidative damage of macromolecules has been suggested to play an important role in the development of AD; however, the underlying mechanism is still unclear. In this study, we showed that the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, was decreased in red blood cells from male AD patients compared with age- and gender-matched controls. However, there was no difference in blood GSH concentration between the female patients and female controls. The decrease in GSH content in red blood cells from male AD patients was associated with reduced activities of glutamate cysteine ligase and glutathione synthase, the two enzymes involved in de novo GSH synthesis, with no change in the amount of oxidized glutathione or the activity of glutathione reductase, suggesting that a decreased de novo GSH synthetic capacity is responsible for the decline in GSH content in AD. These results showed for the first time that GSH metabolism was regulated differently in male and female AD patients.
Liu
Honglei
H
Department of Environmental Health Sciences, School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, AL 35294-0022, USA.
Harrell
Lindy E
LE
Shenvi
Swapna
S
Hagen
Tory
T
Liu
Rui-Ming
RM
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000704:Analysis of Variance; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D004912:Erythrocytes / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000097:blood; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000097:blood; D005981:Glutathione Synthase / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008609:Mental Status Schedule; D012727:Sex Characteristics
D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione; D019803:Glutathione Disulfide