Peroxiredoxin 6 in human brain: molecular forms, cellular distribution and association with Alzheimer's disease pathology.
Peroxiredoxin 6 is an antioxidant enzyme and is the 1-cys member of the peroxiredoxin family. Using two-dimensional electrophoresis and Western blotting, we have shown for the first time that, in human control and brain tissue of patient's with Alzheimer's disease (AD), this enzyme exists as three major and five minor forms with pIs from 5.3 to 6.1. Using specific cellular markers, we have shown that peroxiredoxin 6 is present in astrocytes with very low levels in neurons, but not detectable in microglia or oligodendrocytes. In control brains, there was a very low level of peroxiredoxin 6 staining in astrocytes that was confined to a "halo" around the nucleus. In AD, there were marked increases in the number and staining intensity of peroxiredoxin 6 positive astrocytes in both gray and white matter in the midfrontal cortex, cingulate, hippocampus and amygdala. Confocal microscopy using antibodies to A beta peptide, tau and peroxiredoxin 6 showed that peroxiredoxin 6 positive astrocytes are closely involved with diffuse plaques and to a lesser extent with neuritic plaques, suggesting that plaques are producing reactive oxygen species. There appeared to be little astrocytic response to tau containing neurons. Although peroxiredoxin 6 positive astrocytes were seen to make multiple contacts with tau positive neurons, there was no intraneuronal colocalization. In brain tissue of patients with AD, many blood vessels exhibited peroxiredoxin 6 staining that appeared to be due to the astrocytic foot processes. These results suggest that oxidative stress conditions exist in AD and that peroxiredoxin 6 is an important antioxidant enzyme in human brain defenses.
Power
John H T
JH
Department of Human Physiology, School of Medicine, Flinders University, Adelaide 5042, SA, Australia. john.power@flinders.edu.au
Asad
Sana
S
Chataway
Tim K
TK
Chegini
Fariba
F
Manavis
James
J
Temlett
James A
JA
Jensen
Poul H
PH
Blumbergs
Peter C
PC
Gai
Wei-Ping
WP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D054465:Peroxiredoxin VI / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016875:tau Proteins; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI