Differential expression of peroxiredoxin subtypes in human brain cell types

Sarafian, Theodore A.; Verity, M. Anthony; Vinters, Harry V.; Shih, Charles C.-Y.; Shi, Liangru; Ji, Xiang; Dong, Lingpu; Shau, Hungyi

doi:10.1002/(sici)1097-4547(19990415)56:2<206::aid-jnr1>3.0.co;2-x

Cited by 14 publications

(8 citation statements)

References 126 publications

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“…Prx II positivity was found in the vast majority of tumors (in 84%), and Prx II seemed to be expressed to a greater extent that has been reported previously in normal brain tissue, for example in the study of Sarafian [34]. In that study Prx II was found exclusively in neurons and hardly at all in glial cells.…”

Section: Discussionsupporting

confidence: 49%

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Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors

et al. 2010

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BackgroundPeroxiredoxins (Prxs) have recently been suggested to have a role in tumorigenesis.MethodsWe studied the expression of Prx I-VI and their relationship to patient survival in 383 grade II-IV diffuse astrocytic brain tumors.ResultsPrx I positivity was found in 68%, Prx II in 84%, Prx III in 90%, Prx IV in 5%, Prx V in 4% and Prx VI in 47% of the tumors. Prx I and Prx II expression decreased significantly with increasing malignancy grade (p < 0.001 and p < 0.001). Patients with Prx I or Prx II positive tumors were significantly younger than the average age of all the patients (p = 0.014 and p = 0.005). A lower proliferation rate was associated with Prx I and Prx VI positive tumors (p = 0.019 and p = 0.033), and a lower apoptotic rate was found within Prx I and Prx II positive tumors (p < 0.001 and p = 0.007). Patients with Prx I and Prx II positive tumors had a significantly better survival rate than their Prx-negative counterparts (p = 0.0052 and p = 0.0002).ConclusionThe expression of Prx I and Prx II correlates with astrocytic tumor features, such as grade and patient age and proliferation activity (Prx I), and accordingly with patient survival.

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Section: Discussionsupporting

confidence: 49%

“…In normal mammalian brain immunoreactivity for Prx II has been found principally in the cytosol of most neurons of grey matter [9,34,35]. It has also been found in the nuclei of medial habenular neurons [9].…”

Section: Discussionmentioning

confidence: 99%

Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors

et al. 2010

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“…Moreover, PRX2 is abundantly expressed in murine brain cells that utilize oxygen at high rates (Sarafian et al, 1999; Jin et al, 2005). DA neurons are notorious for their vulnerability to oxidative stress, partly due to their higher rate of oxygen metabolism.…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin-2 Protects against 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration via Attenuation of the Apoptosis Signal-Regulating Kinase (ASK1) Signaling Cascade

Hu¹,

Weng²,

Chu³

et al. 2011

J. Neurosci.

136

108

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The peroxiredoxin (PRX) family of antioxidant enzymes helps maintain the intracellular reducing milieu and suppresses apoptosis in non-neuronal cells. However, whether PRX can inhibit neuronal apoptosis through specific signaling mechanisms remains poorly understood. Induction of PRX2, the most abundant neuronal PRX, occurs in Parkinson's disease (PD) patient brains, but its functional impact is unclear. In the present study, we used the dopaminergic (DA) toxin 6-hydroxydopamine (6-OHDA) to model PD and explore the protective effect and mechanisms of PRX on DA neurons. Of the 2-cysteine PRXs that were tested in MN9D DA neurons, endogenous PRX2 was most beneficial to cell survival. Lentivirus-mediated PRX2 over-expression conferred marked in vitro and in vivo neuroprotection against 6-OHDA toxicity in DA neurons, and preserved motor functions involving the dopamine system in mouse. In addition to its role as an antioxidant enzyme, PRX2 exhibited anti-apoptotic effects in DA neurons via suppression of ASK1-dependent activation of the JNK/c-Jun and p38 pro-death pathways, which are also activated in DA neurons of post-mortem PD brains. PRX2 inhibited 6-OHDA-induced ASK1 activation by modulating the redox status of the endogenous ASK1 inhibitor thioredoxin (Trx). PRX2 over-expression maintained Trx in a reduced state by inhibiting the cysteine thiol-disulfide exchange, thereby preventing its dissociation from ASK1. This study describes a previously undefined mechanism by which redox-sensitive molecules signal via apoptotic pathways in response to PD-relevant toxic stress in DA neurons. Our results also suggest that PRX2 and ASK1 may be potential targets for neuroprotective intervention in PD.

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“…PRX-1 is ubiquitously expressed predominantly in the cytosol and alternatively in nucleus. In brain, PRX-1 is localized to astrocytes, whereas PRX-2 is expressed in neurons (Sarafian et al, 1999). Transfection studies show that PRX-1 can regulate ROS induced by growth factor signaling and can eliminate peroxides in vivo (Kang et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Alterations in brain antioxidant enzymes and redox proteomic identification of oxidized brain proteins induced by the anti-cancer drug adriamycin: implications for oxidative stress-mediated chemobrain

et al. 2010

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Adriamycin (ADR) is a chemotherapeutic for the treatment of solid tumors. This quinone-containing anthracycline is well known to produce large amounts of reactive oxygen species (ROS) in vivo. A common complaint of patients undergoing long-term treatment with ADR is somnolence, often referred to as "chemobrain." While ADR itself does not cross the blood brain barrier (BBB), we recently showed that ADR administration causes a peripheral increase in tumor necrosis factor α (TNF-α), which migrates across the BBB and leads to inflammation and oxidative stress in brain, most likely contributing to the observed decline in cognition. In the current study, we measured levels of the antioxidant glutathione (GSH) in brains of mice injected intraparitoneally (i.p.) with ADR, as well as the levels and activities of several enzymes involved in brain GSH metabolism. We observed significantly decreased GSH levels, as well as altered GSH/GSSG ratio in brains of ADR treated mice relative to saline-treated controls. Also observed in brains of ADR treated mice were increased levels of glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). We also observed increased activity of GPx, but a significant reduction in GST and GR activity in mice brain, 72 hrs post i.p injection of ADR (20 mg/kg body weight). Furthermore, we used redox proteomics to identify specific proteins that are oxidized and/or have differential levels in mice brains as a result of a single i.p. injection of ADR. Visinin like protein 1 (VLP1), peptidyl prolyl isomerase 1 (Pin1), and syntaxin 1 (SYNT1) showed differential levels in ADR treated mice relative to salinetreated controls. Triose phosphate isomerase (TPI), enolase, and peroxiredoxin 1 (PRX-1) showed significantly increased specific carbonylation in ADR treated mice brain. These results further support the notion ADR induces oxidative stress in brain despite not crossing the BBB, and that antioxidant intervention may prevent ADR-induced cognitive dysfunction.

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Differential expression of peroxiredoxin subtypes in human brain cell types

Cited by 14 publications

References 126 publications

Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors

Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors

Peroxiredoxin-2 Protects against 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration via Attenuation of the Apoptosis Signal-Regulating Kinase (ASK1) Signaling Cascade

Alterations in brain antioxidant enzymes and redox proteomic identification of oxidized brain proteins induced by the anti-cancer drug adriamycin: implications for oxidative stress-mediated chemobrain

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