Upregulation of Peroxiredeoxin III in the Hippocampus of Acute Immobilization Stress Model Rats and the Foxo3a-Dependent Expression in PC12 Cells

Abstract

Stress induces structural plasticity in neurons of the adult central nervous system (CNS) and alters the levels of cellular production of reactive oxygen species (ROS), and these changes might involve modifications of the antioxidant defense system. This study investigated whether acute stress altered the expression pattern of peroxiredoxin (Prx) III, which is an antioxidant enzyme that controls cytokine-induced peroxide levels. Prx III immunoreactivity was upregulated in the pyramidal neurons of the hippocampus and in the motor neurons of the spinal cord in an acute immobilization stress (AIS) model. In addition, we tested whether the transcription factor Foxo3a was necessary for the expression of Prx III. The depletion of Foxo3a led to a marked reduction of Prx III and a compensatory enhancement of mitochondrial superoxide dismutase (Mn-SOD) in PC12 cells. The results of this study suggest that Foxo3a mediates the neuronal levels of expression of Prx III and the levels of expression of Mn-SOD in mitochondria. These mechanisms may play an important role in neuroprotection against oxidative stress. Furthermore, Prx III upregulation might be an useful approach for the management of stress.

Mitochondrial Stress Signaling Promotes Cellular Adaptations

“…For instance, the oxidised lipid metabolite 4-hydroxynonenal promotes NRF2 activation of the ARE inducing expression of antioxidant genes [72]. In addition to ARE, ROS activates the transcription factor FOXO3a [73], which induces expression of MnSOD [74] catalase [75] and PrxIII [76] which have antioxidant functions in the mitochondria. Overall, these responses are protective against oxidative damage suggesting that low-grade ROS constitutes an important stress signal that can lead to adaptations that ameliorate a major insult later and protect against disease processes.…”

Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells

“…Prxs are a recently characterized family of antioxidant enzymes, which control the expression levels of cytokine-induced peroxide and mediate signal transduction in mammalian cells (16). Multiple mammalian Prxs (I-VI) often coexist in the same cell in various intracellular locations and function as scavengers of cellular H 2 O 2 , which are released following stimulation with growth factors during proliferation, apoptosis or oxidative stress (17,18). Furthermore, the expression levels of Prxs are high in the heart and there has been increasing interest in their importance in the cardiac response to oxidative stress (19).…”

Upregulation of peroxiredoxin III in doxorubicin-induced cytotoxicity and the FoxO3a-dependent expression in H9c2 cardiac cells

“…Several antioxidants, including peroxiredoxins (Prxs), are components of a ubiquitous thioredoxin-dependent antioxidant defense system, which catalyzes ROS inactivation in mammalian cells (5)(6)(7). Frequently, multiple mammalian Prxs (including Prx I to VI) coexist in various intracellular locations in the same cell (8,9). These act as scavengers of cellular H 2 O 2 that is released following stimulation with various growth factors during apoptosis, oxidative stress or proliferation (8,9).…”

“…Frequently, multiple mammalian Prxs (including Prx I to VI) coexist in various intracellular locations in the same cell (8,9). These act as scavengers of cellular H 2 O 2 that is released following stimulation with various growth factors during apoptosis, oxidative stress or proliferation (8,9). In particular, Prx III has been demonstrated to exhibit a protective role in cisplatin-and gentamicin-induced apoptosis through a mitochondria-dependent pathway (10).…”