Peroxiredoxin 6 in human brain: molecular forms, cellular distribution and association with Alzheimer’s disease pathology

Abstract

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 Aβ 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.

Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders

“…Finally, Prdx6 is almost exclusively expressed in astrocytes, with very low levels appearing in a few large neurons. This Prdx6 expression pattern was also described in human brain (Power et al, 2008) and more recently in rat (AonBertolino et al, 2011) and mouse brain (Godoy et al, 2011). Prdx6 expression in human neurons appeared to be high in the study by Dammeyer and Arnér (2011), although glial expression is also clearly present.…”

Peroxiredoxin I and II in Human Eyes

“…The role of iron in the induction of oxidative stress via the Fenton reaction has been extensively studied in other neoplastic lesions. Many cells and tissues can respond to elevated levels of ROS by increasing the expression and synthesis of protective antioxidant enzymes, such as superoxide dismutase (Usui et al 2009;Lin et al 2005), glutathione peroxidase (Power and Blumbergs 2009) and peroxiredoxin VI (Power et al 2008) In this work, we have investigated the distribution of the two protective antioxidant enzymes peroxiredoxin I and II in the normal human eye. In addition, we have investigated the distribution of these enzymes in pterygia, where we relate increased expression and cellular protection in response to cellular oxidative DNA damage.…”

Microglia antioxidant systems and redox signalling

“…In this respect, Prx 6 occupies a special position, as it is a bifunctional enzyme containing both GSH peroxidase and phospholipase A 2 (PLA 2 ) activities. Prx 6 is primarily expressed in astrocytes (Table 1); (Power et al, 2008) but is up-regulated in activated microglia and macrophages. This correlates with increased expression levels in Alzheimer's disease, and in Prx 6-overexpressing mice, the progression of memory impairment and CNS pathology of Alzheimer disease models is accelerated due to increased oxidative stress (Yun et al, 2013).…”