Disease relevance of PRX1

• Hemolysate thioredoxin reductase and glutathione peroxidase activities correlate with serum selenium in a group of New Zealand men at high prostate cancer risk [1].

High impact information on PRX1

• This is the first example of 1-Cys Prx that has thioredoxin peroxidase activity [2].
• We show also that Prx1p has peroxide reductase activity in vitro using the yeast mitochondrial thioredoxin system as electron donor [2].
• Finally, exposure of null Prx1p mutant cells to oxidant conditions reveals an important role of the mitochondrial 1-Cys Prx in protection against oxidative stress [2].
• Peroxiredoxins (Prxs) have been classified in two groups dependent on the presence of either one (1-Cys Prx) or two (2-Cys Prx) conserved cysteine residues [2].
• Here we show that Trr1 is required during normal cell growth, whereas there is no apparent requirement for Glr1 [3].

Biological context of PRX1

• Angiotensin II, focal adhesion kinase, and PRX1 enhance smooth muscle expression of lipoma preferred partner and its newly identified binding partner palladin to promote cell migration [4].
• Prx1p is located in mitochondria, and it is overexpressed when cells use the respiratory pathway, as well as in response to oxidative stress conditions [2].
• The 1-Cys Prx cDNA (837 bp, accession no. AY870325) contains an open reading frame encoding a protein of 223 amino acid residues with calculated molecular mass of 25,081 Da [5].
• Thioredoxin reductase, an enzyme implicated in the growth, survival and pathogenicity of certain microbes, could be a potential target for therapeutic intervention in Pneumocystis infection [6].
• We have characterized the thioredoxin reductase (trr1) genes from Pneumocystis carinii and Pneumocystis jiroveci, and have demonstrated that multiple copies of an approximately 500 base pair fragment of the trr1 gene are present in P. carinii, but not in P. jiroveci [6].

Anatomical context of PRX1

• Doxorubicin alone, depleted reductive capacity, i.e. decreased the activity of thioredoxin reductase in the skin, as well as the content of reduced glutathione both in the skin and blood plasma [7].

Associations of PRX1 with chemical compounds

• We have previously shown that glucose represses the expression of mitochondrial thioredoxin peroxidase gene (PRX1) in a process mediated by cAMP/protein kinase A (PKA) and Msn2/4p [8].
• Finally, mTPx I also induced by t-butyl hydroperoxide in a Hap1p-independent manner [9].
• Independent of dietary Se chemical form, thioredoxin reductase activity was responsive to reproductive state [10].
• Here, for the first time in a pathogenic eukaryote, we have demonstrated that the amoebic protein also possesses peroxidatic and antioxidant activities in the presence of reductants such as dithiothreitol or thioredoxin reductase plus thioredoxin [11].
• The antigenicity was lost upon reduction of TR by NADPH indicating a large conformational change upon reduction of the redox-active disulfide in the enzyme [12].

Other interactions of PRX1

• We also identified the position of the stress transcription responsive element (STRE) in the PRX1 promoter, which is recognized by Msn2p and Msn4p activators [8].
• Expression of mitochondrial thioredoxin peroxidase (Prx1p) from Saccharomyces cerevisiae is subjected to complex transcriptional regulation and is responsive to the levels of several compounds such as glucose and peroxides [8].
• The antioxidant activity of 1-Cys Prx was tested for its ability to protect yeast enolase against inactivation of the mixed-function oxidation system [13].

References