Disease relevance of Prdx5

• Adult rat liver contained variant forms of thioredoxin reductase with isoelectric points at pH 4.9 and at approximately pH 4.7 compared to pH 5.1 for the enzyme from Novikoff ascites hepatoma [1].
• The reduction in steady-state mRNA levels for SR phospholamban (PLP) and Ca2+ release channel (CRC) in the pressure-overloaded animals was also prevented without any reduction in the extent of cardiac hypertrophy by treatment with etomoxir [2].
• The intracerebroventricular injection of pyridoxal phosphate (PLP, 0.125-1.25 mumol/rat) causes epileptic seizures (4 min leads to 1 min) that are preventable or reversible by GABA (1 mumol/rat), by muscimol (0.025 mumol/rat), or by diazepam (1.75 mumol/rat) [3].
• The holo-SDH contained PLP-OMS aldimine in the active site, indicating that OMS can form the Schiff base linkage with PLP, but the subsequent dehydration did not occur [4].
• We found that the number of PLP-exon-3b labelled cells remained constant during the course of Wallerian degeneration while the number of cells labelled with the riboprobes to PDGFRalpha and MOG increased [5].

High impact information on Prdx5

• Similar beneficial effects of etomoxir treatment were also evident when the gene expression for SR SERCA2, PLP, and CRC in the hypertrophied heart was normalized with respect to mRNA for GAPDH [2].
• This gradient along the nerve of oligodendrocyte differentiation continues with oligodendrocytes near the chiasm expressing the genes and encoded proteins to MBP and PLP 3 d before oligodendrocytes near the eye [6].
• Here, we demonstrate that pyridoxal phosphate (PLP) is a linear and reversible inhibitor of ACC-1 and ACC-2 [7].
• The activity was completely restored by dithiothreitol or thioredoxin with a reducing system containing thioredoxin reductase and NADPH, but glutathione did not restore the activity [8].
• Pre-treatment with citrate increased the apparent Ki for ACC inhibition by PLP by approximately 4-fold [7].

Chemical compound and disease context of Prdx5

• Since the duration of PLP-induced epileptic seizures is short and can be prevented by GABA agonists, PLP may be used as a tool to study the nature of GABA-mediated neuroinhibition and the properties of GABA receptor sites [3].
• PLP induced barrel turning, running fits and tonic-clonic convulsions, which started 5-10 min after recovery from the anesthesia (halothane), peaked at 20 min and disappeared at about 50 min [9].
• Plasma PLP, tryptophan-load test results, food intake, and tissue and body weights were not different at wk 6 [10].

Biological context of Prdx5

• The cDNA coded for a protein of 48 kDa containing the sequence Ser-Ala-Gly-Lys-Ser-Phe, which corresponds closely to the PLP binding site in other PLP-containing enzymes [11].
• The inhibition of intestinal PLP hydrolysis may possibly be one of the mechanisms by which a high percentage of alcoholics become biochemically vitamin B6 deficient [12].
• Mammalian thioredoxin reductase (TrxR) is important for cell proliferation, antioxidant defense, and redox signaling [13].
• This study focuses on the presence of and subcellular localisation of thioredoxin reductase in a tumor model where neoplastic lesions are selected by their resistance to the toxic effects of the promotor [14].
• Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress [15].

Anatomical context of Prdx5

• Specificity for thioredoxin reductase was indicated by loss of activity in dialyzed cytosol prepared from livers of selenium-deficient rats, by inhibition with aurothioglucose at concentrations selective for thioredoxin reductase, and by stimulation with selenocystine [16].
• Furthermore, expression of HGF was significantly increased in the peritoneum of PLP-treated rats compared with that of PD-treated rats [17].
• PLP-dependent enzyme activity in the midbrain increases in parallel with increased expression of GAD65 mRNA in the striatum [18].
• The previous in vitro studies have shown that PLP increases the uptake of [3H]GABA into synaptosomes and inhibits the binding of [3H]GABA to synaptic membranes [3].
• As a consequence of this, GABA levels in cerebral cortex decrease, since synthesis of GABA is determined by glutamate decarboxylase, a PLP-dependent enzyme [19].

Associations of Prdx5 with chemical compounds

• GABA synthesis in the nominal absence of PLP was enhanced by malate (twofold increase at 5 mM) and citrate (threefold increase at 5 mM), but was unaffected by ATP and chloride [20].
• Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase [16].
• Comparison of the kinetic properties of the cytosolic and microsomal forms of the enzyme showed that their Km for glutamate was the same, but that the cytosolic GAD had a lower Km for PLP [20].
• However, if the islet homogenate was prepared and incubated in the presence of PLP, neither malate nor citrate influenced enzyme activity [20].
• Dehydroascorbic acid is generated by dismutation of the ascorbyl free radical, and thioredoxin reductase can reduce dehydroascorbic acid to ascorbate [16].

Other interactions of Prdx5

• Thioredoxin reductase had a Km of 2.5 microM for rat and calf liver thioredoxin and a Kcat of 3000 min-1 [21].
• Consequently, this study was undertaken to evaluate the effect of sustained high serum insulin levels on the activity of hepatic catalase, a peroxisomal antioxidant enzyme involved in the decomposition of H2O2 [22].

Analytical, diagnostic and therapeutic context of Prdx5

• ACC from rat liver was equally sensitive to PLP following extensive purification by avidin affinity chromatography [7].
• Molecular cloning and characterization of a mitochondrial selenocysteine-containing thioredoxin reductase from rat liver [23].
• Models included PLP decay during in vitro incubation and PLP luminal disappearance during in vivo perfusion of jejunal segments [12].
• Concomitantly, as investigated by RT-PCR analysis, the transcriptional activity of c-fos and c-jun was stimulated, without altering mRNA expression of the myelin-specific genes MBP, MAG, and PLP [24].
• Adrenalectomy resulted in decreased conversion of dietary vitamin B6 to PLP [19].

References