Disease relevance of Prdx2

• Murine erythroleukemia cells (MEL cells) increased TPx transcription when in a chemically differentiated state [1].
• Furthermore, expression of mouse TPx in PC12 pheochromocytoma cells prolonged their survival in the absence of nerve growth factor (NGF) and serum, indicating that TPx could promote neuronal cell survival [1].
• 025 mg ATG/g body weight caused significant and prolonged inhibition of TR activity in all tissues examined [2].
• Histopathological and immunohistochemical studies using antibodies against PrxI/PrxII/GPxI were carried out on specimens from four different strains of animal models of mutant SOD1-linked familial amyotrophic lateral sclerosis (ALS) [3].
• Thioredoxin reductase induction coincides with melanin biosynthesis in brown and black guinea pigs and in murine melanoma cells [4].

Psychiatry related information on Prdx2

• Multiple myelomas produce tumor-specific antigen (TSA) in the form of idiotype (Id) on monoclonal Ig [5].

High impact information on Prdx2

• However, because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec antigen presentation or indirectly by thymic bone marrow (BM)-derived cells via cross-presentation [6].
• METHODS: BALB/cAnCr mice were inoculated with syngeneic parental mammary adenocarcinoma (TSA) cells in quantities sufficient to lead to tumors in all inoculated mice [7].
• They are reduced by NADPH via Trx reductase (TR) or oxidized GSH (GSSG) reductase and further supply electrons for deoxyribonucleotide synthesis, antioxidant defense, and redox regulation of signal transduction, transcription, cell growth, and apoptosis [8].
• This unusual substrate specificity is achieved by an evolutionary conserved fusion of the TR and glutaredoxin domains [8].
• Thus, a TSA can be transferred in vivo from myeloma, and possibly other types of cancer cells to APC for MHC class II presentation to CD4(+) T cells [5].

Chemical compound and disease context of Prdx2

• Azelaic acid as a competitive inhibitor of thioredoxin reductase in human melanoma cells [9].
• (R)-Trichostatin A (TSA) is a Streptomyces product which causes the induction of Friend cell differentiation and specific inhibition of the cell cycle of normal rat fibroblasts in the G1 and G2 phases at the very low concentrations [10].
• Therefore, tumor cells TSA, J558L, EB, and ESB and, as a control, NIH-3T3 cells were infected with a retrovirus containing a hygromycin/TK fusion gene [11].
• A novel strain, Origami(DE3), of Escherichia coli with mutations in the glutathione and thioredoxin reductase genes yielded 60% more soluble PvMSP-1 p42 than the conventional E. coli BL21(DE3) strain [12].
• In P388 leukemia, dose for dose, at 4 hr, 6-diazo-5-oxo-L-norleucine (NSC-7365) (DON) was the most potent of the L-glutamine antagonists in elevating basal PRPP pool size (50% above control) followed by AT-125 and azaserine, 300 and 100% above control respectively [13].

Biological context of Prdx2

• Murine thioredoxin peroxidase delays neuronal apoptosis and is expressed in areas of the brain most susceptible to hypoxic and ischemic injury [1].
• Mouse TPx had broad tissue distribution, but its expression was especially marked in cells that metabolize oxygen molecules at high levels such as erythroid cells, renal tubular cells, cardiac and skeletal muscle cells, and certain types of neurons [1].
• We cloned the cDNA encoding the mouse homolog of TPx from an E14.5 brain cDNA library and analyzed its distribution and function in murine tissues [1].
• Comparison of the amino acid sequence of mouse TPx with those of other species revealed that TPx was highly conserved across all species [1].
• Such inhibition of TR could lead to increased levels of oxidative stress in vivo, thereby increasing the virulence of several viruses including the coxsackievirus [2].

Anatomical context of Prdx2

• We propose that TPx contributes to antioxidant defense in erythrocytes and neuronal cells by limiting the destructive capacity of oxygen radicals [1].
• In the presence of low serum concentrations, PrxII-deleted T cells proliferate more vigorously after stimulation with concanavalin A [14].
• The increased number ofthymocytes in PrxII-null thymus is related to reduced hypodiploid cell formation [14].
• At the end stage, near normal PrxI/PrxII/GPxI expression was observed again in the hepatocytes [3].
• Thioredoxin peroxidase secreted by Fasciola hepatica induces the alternative activation of macrophages [15].

Associations of Prdx2 with chemical compounds

• Concomitantly with a rise in oxidant levels, antioxidant defenses were decreased, including total glutathione content and the activity of glutathione peroxidase, whereas thioredoxin reductase activity was not changed [16].
• The amount of apoptosis, induced by food restriction orby the injection of dexamethasone, is consistently lower in PrxII-null thymocytes than in wild-type thymocytes [14].
• Aurothioglucose inhibits murine thioredoxin reductase activity in vivo [2].
• The DKO cells had lower (P < 0.05) microsomal cytochrome P450 2E1 activities, but higher (P < 0.05) glutathione reductase and thioredoxin reductase activities than the WT cells at 0 hrs, and they responded differently to the APAP and NAPQI treatments [17].
• Our findings also suggest that thioredoxin reductase and gamma-glutamylcysteine synthase belong to the same synexpression group [18].

Regulatory relationships of Prdx2

• In vitro studies showed that this recombinant TPx directly converts RAW 264.7 macrophages to an alternatively activated phenotype characterized by the production of high levels of interleukin-10 (IL-10), prostaglandin E(2), corresponding with low levels of IL-12 [15].

Other interactions of Prdx2

• In liver and heart, some recovery of TR activity was observed after a 7-d period, but no recovery was observed in pancreas or kidney [2].
• Serum BAFF protein level and BAFF transcript expression in splenocytes were significantly higher in PrxII(-/-) mice than wildtype mice [19].
• Our results suggest that both tyrosinase and thioredoxin reductase respond to oxidative stress in the epidermis as well as in melanoma cells and react with superoxide anion radicals to stimulate melanogenesis and to prevent peroxidative damage, respectively [4].
• Loss of activity of the selenoenzyme thioredoxin reductase causes induction of hepatic heme oxygenase-1 [20].
• The mouse Aop2 (antioxidant protein 2) cDNA recently cloned from liver and kidney is a member of the thiol-specific antioxidant gene family [21].

Analytical, diagnostic and therapeutic context of Prdx2

• (75)Se-labeling, Western blot analysis, and enzymatic activities revealed that transgenic mice have reduced (P < 0.05) liver and colon glutathione peroxidase expression, but conserved thioredoxin reductase expression compared with wild-type mice, regardless of selenium status [22].
• Structural features of these genes and the results of RT-PCR analysis on RNAs from various tissue sources indicate that the Prx II-2 and Prx II-3 genes could be pseudogenes derived from the Prx II-1 gene by a mechanism involving retrotransposition [23].
• The functional status of the thioredoxin/thioredoxin reductase system during in vivo chemoprevention with Se has not been established [24].
• Only two of 20 mice with 7-day-old TSA tumors were cured by vaccination with proliferating TSA-IL12 cells, whereas 24 of 30 mice with such tumors were cured by intraperitoneal administration of rIL-12 [7].
• In situ hybridization showed IL-15 expression in C26/12 but not in TSA/12 tumors [25].

References