Disease relevance of Prdx1

• Treatment of primary rat hepatocyte or hepatoma cell cultures with the heavy metals CdCl2 (10 microM) and CoCl2 (300 microM) induced in parallel HBP23 and HO-1 mRNA levels, in the case of CdCl2 to even higher levels than heme [1].

Psychiatry related information on Prdx1

• HBP23 was constitutively expressed in KC and up-regulated on the protein and messenger RNA (mRNA) level by LPS with a time response distinct from that of TNFalpha, but in coordination with that of heme oxygenase-1 (HO-1), which is the inducible isoform of the rate-limiting enzyme of heme degradation [2].

High impact information on Prdx1

• Several significant structural differences have been found from a 1-Cys peroxiredoxin, ORF6, which lacks the C-terminal conserved cysteine corresponding to Cys-173 of HBP23 [3].
• The active site is largely hydrophobic with partially exposed Cys-173, suggesting a reduction mechanism of oxidized HBP23 by thioredoxin [3].
• The induction of HBP23 mRNA expression by LPS was preceded by that of the inducible nitric oxide synthase (iNOS) and the production of nitrite in KC [2].
• Because lipopolysaccharide (LPS) stimulates macrophages to produce large amounts of ROS the gene expression of HBP23 was analyzed during treatment with LPS in cultured rat Kupffer cells (KC) [2].
• The data suggest that NO and peroxynitrite are major mediators of the LPS-dependent up-regulation of HBP23 in KC [2].

Biological context of Prdx1

• Complementary regulation of heme oxygenase-1 and peroxiredoxin I gene expression by oxidative stress in the liver [4].
• The mRNA levels of the HO-1 and Prx I genes were induced in whole livers of CCl4-treated rats with differential kinetics as determined by Northern blot analysis [4].
• An increase in HBP23 mRNA was observed in Hepa 1-6 cells after treatment with heme and cadmium and during liver regeneration after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)[5]
• To investigate the regulatory role of cellular phosphorylation and dephosphorylation events on hepatic HBP23/Prx I gene expression, primary cultures of rat hepatocytes were treated with okadaic acid (OA) which is a specific inhibitor of the serine threonine protein phosphatases 1 and 2A [6].
• In addition, down-regulation of the chaperone-like protein, glucose-regulated protein 78, was consistent with the decreased expression of the secretory proteins serum paraoxonase, serum albumin, and peroxiredoxin IV [7].

Anatomical context of Prdx1

• CCl4-dependent oxidative stress led to a focal increase of perivenous HO-1 positive liver cells with simultaneous loss of Prx I immunoreactivity [4].
• A 23-kDa protein with high affinity for heme (KD = 55 nM), therefore termed heme-binding protein 23 kDa (HBP23), was purified from rat liver cytosol [Iwahara, S., et al. (1995) Biochemistry 34, 13398-13406] [1].
• As determined by immunocytochemical (ICC) studies in liver cell cultures and by Western and Northern blotting analysis, HBP23/Prx I was highly expressed in cultures of isolated hepatocytes and Kupffer cells [8].
• By immunoelectron microscopy using the protein A-gold technique, HBP23/Prx I immunoreactivity was detected in cytoplasm, nuclear matrix, mitochondria, and peroxisomes of parenchymal and non-parenchymal liver cell populations [8].
• A parallel up-regulation of HBP23 and HO-1 mRNA by LPS was also observed in cultured peritoneal macrophages and peripheral blood monocytes [2].

Associations of Prdx1 with chemical compounds

• Moreover, expression of the HO-1 and Prx I genes was determined in a model of acutely damaged rat liver which was elicited by application of a single dose of carbon tetrachloride (CCl4) [4].
• HBP23 mRNA induction by LPS occurred on the transcriptional level as indicated by blocking with actinomycin D [2].
• Both the nitric oxide (NO)-donor S-nitroso-N-acetylpenicillamine and the peroxynitrite donor SIN-1 increased HBP23 mRNA expression [2].
• Up-regulation of heme-binding protein 23 (HBP23) gene expression by lipopolysaccharide is mediated via a nitric oxide-dependent signaling pathway in rat Kupffer cells [2].
• Treatment with the NOS inhibitor NG-monomethyl L-arginine prevented HBP23 mRNA induction by LPS, which was reversed by an excess of L-arginine [2].

Regulatory relationships of Prdx1

• HBP23 mRNA induction by LPS was down-regulated by interleukin 10 and transforming growth factor beta1 with a NO-independent mechanism [2].

Other interactions of Prdx1

• While HO-1 mRNA was induced up to 48 hr, Prx I exhibited a maximum level of mRNA after 12 hr of treatment with CCl4 [4].
• HBP23/Prx I induction by OA occurred on the transcriptional level as determined by studies with actinomycin D and nuclear run-off assays [6].
• Immunodepletion of the 28-kDa peroxiredoxin profoundly decreased the antioxidant activity of the olfactory tissue extract [9].
• However, by using matrix-assisted laser dissociation/ionization time-of-flight mass spectrometry (MALDI-TOF MS), we identified several other proteins which are susceptible to S-nitrosylation in liver microsomes, including retinol dehydrogenase type I (RODH I), aldolase B, cytochrome P4502C11, and peroxiredoxin 1 [10].

Analytical, diagnostic and therapeutic context of Prdx1

• In both cell cultures HBP23 mRNA levels were upregulated in a time- and dose-dependent manner by heme [1].
• Whereas by immunohistochemistry (IHC) a uniformly high level of HBP23/Prx I expression was observed in liver parenchymal and different sinusoidal cells, HO-1 expression was restricted to Kupffer cells [8].
• In situ hybridization with 33P-labeled antisense RNA probe revealed the expression of the 28-kDa peroxiredoxin mRNA in tissues with a high level of the 28-kDa peroxiredoxin immunoreactivity [9].
• By immunoblotting, the 28-kDa peroxiredoxin was found to be most highly concentrated in olfactory epithelium and present in all tissues tested (skin, lung, trachea, kidney, womb, and brain) [9].
• Patterns of expression of the 2-Cys and 1-Cys peroxiredoxin (Prx) proteins of the rodent malaria parasite Plasmodium yoelii during its life cycle were observed by immunofluorescent antibody staining and confocal laser scanning microscopy [11].

References