Expression and Changes of Hyperoxidized Peroxiredoxins in Non-Pyramidal and Polymorphic Cells in the Gerbil Hippocampus During Normal Aging

Abstract

Oxidative stress is one of predisposing factors to age-related neurodegeneration in the brain. In particular, thiol-containing groups are susceptible to oxidative stress, which induces the formation of the disulfide bond and/or hyperoxidized form of thiol-containing proteins. We observed the protein thiol levels in the hippocampal homogenates and also investigated changes in hyperoxidized form of peroxiredoxin (Prx-SO(3)) immunoreactivity and proteins levels in the gerbil hippocampal subregions during normal aging. Levels of total thiol, non-protein thiol, and protein thiol were decreased in the hippocampal homogenates with age. At post-natal month 1 (PM 1), pyramidal and non-pyramidal cells in the hippocampal CA1 region (CA1) showed Prx-SO(3) immunoreactivity. Prx-SO(3) immunoreactivity in the cells was decreased by PM 12, thereafter, Prx-SO(3) immunoreactivity in the cells increased again with age. In the CA2/3, Prx-SO(3) immunoreactivity in pyramidal cells was not significantly changed; however, the immunoreactivity in pyramidal cells was very low at PM 12. Prx-SO(3) immunoreactivity in the dentate gyrus (DG) was distinctly changed during aging. At PM 1, Prx-SO(3) immunoreactivity in granule and polymorphic cells was weak and strong, respectively. The immunoreactivity in the neurons was decreased with age, not shown in any neurons at PM 12. Thereafter, Prx-SO(3) immunoreactivity increased again with age. In addition, Prx-SO(3) protein level in the hippocampus was lowest at PM 12. These results suggest that thiol-containing proteins are changed during aging and Prx-SO(3) immunoreactivity was different according to cells in the hippocampal subregion during aging.

Role of histone acetylation in the activity-dependent regulation of sulfiredoxin and sestrin 2

“…The hyperoxidation of Prxs may also take place in the brain in response to a variety of oxidative trauma: we recently found that an episode of ischemia, followed by reperfusion, induces strong hyperoxidation of Prxs in the mouse cortex 12. Increased levels of hyperoxidized Prxs have also been observed during normal aging in the gerbil hippocampus 13…”

“…Sometimes, under increased oxidative stress, Prx-SOH is further oxidized by peroxide to sulfinic (-SO 2 H) acid, causing inactivation of peroxidase activity 11. Prx hyperoxidation to Prx-SO 2 H takes place in neurons undergoing oxidative death in vitro, and is associated with ischemic brain damage in vivo as well as normal aging 12,13. Prx-SO 2 H is not a substrate for the resolving cysteine and cannot be reduced by thioredoxin.…”

The antioxidant enzyme peroxiredoxin and its protective role in neurological disorders

“…Oxidative modifications of Prx enzymes were observed during normal aging, and closely correlated with age. 40 Neuronal overexpression of Prx2 in Drosophila melanogaster was found to attenuate oxidative stress and prolong longevity, suggesting Prx2 may function as an antiaging gene. 41 It has been repeatedly shown that altered expression of Prxs occurs in brain tumors though the exact causal role of Prxs in brain tumorigenesis remains to be established.…”

Oxidative stress response and Nrf2 signaling in aging

“…In mitochondria oxidized Prdx3 increased in aged rat liver compared with that of young adults (28 mo vs 12 mo) while the reduced form remained unchanged [119]. The oxidized form of Prdx in hippocampus was lowest at 12 mo and started to increase thereafter [120, 121]. The age-related accumulation of hyperoxidized Prdx appears to be linked to the increase of oxidant production with aging; however, it may also suggest a less efficient Prdx repairing mechanism in senescent cells.…”