Disease relevance of PRDX5

• To determine whether the level of expression was different between multinodular goiters and hyperthyroid Graves' thyroids, PRDX5 immunoblotting was performed in these two respective tissues [1].
• We observed that PRDX5 expression was higher in the thyroid gland of patients with Graves' disease compared to multinodular goiters [1].
• Human AOEB166 shares 63% similarity with Escherichia coli AhpC22 alkyl hydroperoxide reductase and 66% similarity with a recently identified Saccharomyces cerevisiae alkyl hydroperoxide reductase/thioredoxin peroxidase [2].
• Expression and regulation of peroxiredoxin 5 in human osteoarthritis [3].
• It has been shown that melanomas which respond to Fotemustine therapy contain more thioredoxin reductase whereas resistant metastases yielded the opposite result.(ABSTRACT TRUNCATED AT 250 WORDS)[4]

Psychiatry related information on PRDX5

• Decreased thioredoxin and increased thioredoxin reductase levels in Alzheimer's disease brain [5].
• In one diet-controlled crossover study, alcohol consumption resulted in an increase in the plasma vitamin B6 (PLP) content, especially after beer consumption (containing vitamin B6), but also after wine and spirit consumption (not containing vitamin B6) [6].

High impact information on PRDX5

• Recent studies with a human adenocarcinoma cell line led to the unexpected discovery that selenocysteine occurs in mammalian thioredoxin reductase [7].
• Defective metabolism of pyridoxal 5'-phosphate (PLP), characterized by elevated serum PLP levels, results in reduced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain [8].
• The accumulating P6C inactivates pyridoxal 5'-phosphate (PLP) by forming a Knoevenagel condensation product [9].
• MAIN OUTCOME MEASURES--Plasma homocysteine concentration correlated with plasma folate, vitamin B12, pyridoxal-5'-phosphate (PLP), and oral intakes of these vitamins, and the contribution of these vitamins to the prevalence of elevated homocysteine in the population [10].
• Homocysteine demonstrated weaker, inverse associations with plasma vitamin B12 and PLP [10].

Chemical compound and disease context of PRDX5

• We studied the expression of antioxidant enzymes (AOEs) and related proteins manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR), and the catalytic (GLCL-c) and regulatory (GLCL-r) subunits of glutamate cysteine ligase (gamma-glutamylcysteinesynthetase) in 433 astrocytomas [11].
• It is possible that TR expression may be positively regulated by the calcium-signalling cascade, although TR induction by A23187 may be due to toxicity [12].
• Thioredoxin reductase in human hepatoma cells is transcriptionally regulated by sulforaphane and other electrophiles via an antioxidant response element [13].
• 13-cis retinoic acid has been shown to be a stereospecific suicide inhibitor of thioredoxin reductase purified from human melanoma tissue [14].
• The stereospecific suicide inhibition of human melanoma thioredoxin reductase by 13-cis-retinoic acid [14].

Biological context of PRDX5

• Functionally, PRDX5 has been implicated in antioxidant protective mechanisms as well as in signal transduction in cells [15].
• The present study suggests that PRDX5 may play a protective role against oxidative stress in human cartilage [3].
• Overexpression of PRDX5 in human tendon cells via transfection inhibited H(2)O(2)-induced tendon cell apoptosis by 46% (P<0.05), and prevented the decrease in tendon cell collagen synthesis which occurs under H(2)O(2) challenge, although the decrease in collagen synthesis was small [16].
• Of interest, the analysis of N- and C-terminal domains of both human and rat AOEB166 reveals amino acid sequences presenting features of mitochondrial and peroxisomal targeting sequences [2].
• A new function for the TR/T/TPx system in epidermal cells has been discovered in the control of the important cofactor (6R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH(4)) homeostasis [17].

Anatomical context of PRDX5

• Peroxiredoxin 5 (PRDX5) is a novel type of mammalian thioredoxin peroxidase widely expressed in tissues and located cellularly to mitochondria, peroxisomes and cytosol [15].
• The present study demonstrated that normal human tendon expresses PRDX5 and its expression is significantly increased in degenerative tendon [18].
• The analysis of AOEB166 mRNA distribution in 30 different human tissues and in 10 cell lines shows that the gene is widely expressed in the body [2].
• Immunoblot analysis revealed that PrxV is widely expressed in rat tissues and cultured mammalian cells and is localized intracellularly to cytosol, mitochondria, and peroxisomes [19].
• Furthermore, human AOEB166 expressed as a fusion protein with GFP in HepG2 cell line is sorted to these organelles [2].

Associations of PRDX5 with chemical compounds

• In the reduced form of PRDX5, Cys47 and Cys151 are distant of 13.8 A although these two cysteine residues are thought to be involved in peroxide reductase activity by forming an intramolecular disulfide intermediate in the oxidized enzyme [15].
• Systemically administered recombinant PRDX5 provided protection against ibotenate-induced excitotoxic stress [20].
• Two classical antioxidants, N-acetylcysteine and catalase-PEG, provided the same neuroprotective effect as PRDX5 [20].
• The possible role of benzoate in the antioxidant activity of PRDX5 is discussed [15].
• Recombinant PRDX5 plus dithiothreitol displayed a synergistic neuroprotective effect on NMDA-induced neuronal death [20].

Physical interactions of PRDX5

• In KD clones, but not in RD-clones, formation of etoposide-induced gamma-H2AX was increased, indicating that PrxV inhibits conversion of topoisomerase II cleavage complexes into double-strand DNA breaks but this inhibition is not caused by its antioxidant activity [21].

Regulatory relationships of PRDX5

• In conclusion, our data show that PRDX5 is expressed in the thyroid gland where it could act as antioxidant [1].
• Bacterially expressed ACR1 is demonstrated to inhibit RNA polymerase III (Pol III)-dependent Alu transcription in vitro but showed no repression of transcription of a tRNA gene or of a reporter gene under control of a Pol II promoter [22].

Other interactions of PRDX5

• Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 A resolution [15].
• The crystal structure reveals that PRDX5 presents a thioredoxin-like domain [15].
• Here, we show that nuclear PrxV associates with coilin-containing bodies suggesting possible interaction of this protein with transcription complexes [21].
• By HLA-tetramer analysis, in a tumor-invaded lymph node, >50% of mutant Prdx5-specific CD8(+) T cells (frequency 0.37%/CD8(+)) showed a CCR7(+/-) CD45RA(-) "T(CM)" or "T(EM)" phenotype, as found in Melan-A/MART-1-specific T cells (frequency 0.68%/CD8(+)) in the same tissue [23].
• Thioredoxin reductase-alpha and plasma glutathione peroxidase mRNA expression were not altered in adenomas [24].

Analytical, diagnostic and therapeutic context of PRDX5

• Using two-dimensional electrophoresis, we have recently identified in human bronchoalveolar lavage fluid a novel protein, termed B166, with a molecular mass of 17 kDa [2].
• This protein was identified by Western blotting as the redox-active lipid-hydroperoxide-detoxifying selenoprotein, thioredoxin reductase (TR) [12].
• Moreover, with the use of pulse radiolysis, we show that human peroxiredoxin 5 reduces peroxynitrite with an unequalled high rate constant of (7+/-3)x10(7) M(-1)s(-1) [25].
• In cultures of the airway epithelial cell lines (Calu-3, JME), primary airway cell culture (cow), and alveolar epithelial cells A549, CSE also significantly decreased transepithelial electrical resistance and expression of PRXV protein, and induced glutathione and protein oxidation [26].
• Replacement of the SeCys residue by Cys in rat cytosolic thioredoxin reductase using site-directed mutagenesis and expression in Escherichia coli resulted in a functional mutant enzyme having about one percent activity with thioredoxin as a substrate through a major loss of Kcat and a shift in the pH optimum from 7 to 9 [27].

References