• IMMUNE NETWORK
• /
• v.21 no.5
• /
• pp.36.1-36.16
• /
• 2021

Peroxiredoxins (Prxs) are ubiquitously expressed peroxidases that reduce hydrogen peroxide or alkyl peroxide production in cells. Prxs are released from cells in response to various stress conditions, and they function as damage-associated molecular pattern molecules. However, the secretory mechanism of Prxs and their roles have not been elucidated. Thus, we aimed to determine whether inflammasome activation is a secretory mechanism of Prxs and subsequently identify the effect of the secreted Prxs on activation of the classical complement pathway. Using J774A.1, a murine macrophage cell line, we demonstrated that NLRP3 inflammasome activation induces Prx1, Prx2, Prx5, and Prx6 secretion in a caspase-1 dependent manner. Using HEK293T cells with a transfection system, we revealed that the release of Prx1 and Prx2 relies on gasdermin-D (GSDMD)-mediated secretion. Next, we confirmed the binding of both Prx1 and Prx2 to C1q; however, only Prx2 could induce the C1q-mediated classical complement pathway activation. Collectively, our results suggest that inflammasome activation is a secretory mechanism of Prxs and that GSDMD is a mediator of their secretion. Moreover, secreted Prx1 and Prx2 bind with C1q, but only Prx2 mediates the classical complement pathway activation.

• Tuberculosis and Respiratory Diseases
• /
• v.53 no.1
• /
• pp.36-45
• /
• 2002

Background : In mammals, the activity of antioxidant enzymes is increased in adult lung to adapt to hyperoxia. The increase of these activities is augmented in neonates and is known as an important mechanism of tolerance to high oxygen levels. Peroxiredoxin(Prx) is an abundant and ubiquitous intracellular antioxidant enzyme. Prx I and II are major cytosolic subtypes. The aim of this study was to examine th Prx I and II mRNA and protein expression levels in adult rat lungs and to compare then with those of neonatal rat lungs exposed to hyperoxia. Materials and Methods : Adult Sprague-Dawley rats and neonates that were delivered from timed pregnant Sprague-Dawley rat were randomly exposed to normoxia or hyperoxia. After exposure to high oxygen level for a set time, the bronchoalveolar lavage fluid and lung tissue were obtained. The Prx I and II protein expression levels were measured by western blot analysis using polyclonal rabbit anti-Prx I or anti-Prx II antibodies and the relative expression of the Prx I and Prx II per Actin protein were obtained as an internal standard. The Prx I and II mRNA expression levels were measured by northernblot analysis using Prx I and Prx II-specific cDNA prepared from pCRPrx I and pCRPrx II, and the relative Prx I and Prx II expression levels per Actin mRNA were obtained as an internal standard. Results : Hyperoxia induced some peak increase in the Prx I mRNA levels after 24 hour in adult rats. Interestingly, hyperoxia induced a marked increase of Prx I mRNA 24 hour in neonatal rats. However, hyperoxia did not induce an alteration in the expression of Prx II mRNA in both the adult and neonatal rat lungs. Hyperoxia did not induce an alteration in the expression of the Prx I and Prx II protein in both the adult and neonatal rat lungs. Hyperoxia did not induce an alteration in the amount of Prx I and Prx II protein all the times in the bronchoalveolar fluid of adult rats. Conclusion : Prx I and II is differently regulated by hyperoxia in adult and neonatal rat lung at the transcriptional level. The prominent upregulation of Prx I mRNA in neonates compared to those in adults by hyperoxia may be another mechanism of resistance to high oxygen levels in neonate.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.4
• /
• pp.451-459
• /
• 1999

Background : In sepsis, excessive generation of reactive oxygen species plays key roles in the pathogenesis of acute lung injury. The serum antioxidants such as catalase and MnSOD are elevated in sepsis and considered as predictors of acute respiratory distress syndrome(ARDS) and prognostic factors of sepsis. Peroxiredoxin(Prx) has recently been known as an unique and major intracellular antioxidant. In this study, we evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells(RAW 267.7) after treatment of oxidative stress and endotoxin and measured the amount of Prx I, Prx II and thioredoxin(Trx) in peritoneal and bronchoalveolar lavage fluid of septic animal model. Methods : Using immunoblot analysis with specific antibodies against Prx I, Prx II and Trx, we evaluated the distribution of Prx I and Prx II in human neutrophil, alveolar macrophage and red blood cell. We evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide(LPS) and measured the amount of Prx I, Prx II and Trx in peritoneal lavage fluid of intraperitoneal septic animals(septic animal model induced with intraperitoneal 6 mg/Kg LPS injection) and those in bronchoalveolar lavage fluid of intraperitoneal septic animals and intravenous septic animals(septic animal model induced with intravenous 5 mg/Kg LPS injection) and compared with the severity of lung inflammation. Results : The distribution of Prx I and Prx II were so different among human neutrophil, alveolar macrophage and red blood cell. The expression of Prx I in mouse monocyte-macrophage cells was increased after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide but that of Prx II was not increased. The amount of Prx I, Prx II and Trx were increased in peritoneal lavage fluid of intraperitoneal septic animals but were not increased in bronchoalveolar lavage fluid of intraperitoneal and intravenous septic animals regardless of the severity of lung inflammation. Conclusion : As intracellular antioxidant, the expression of Prx I is increased in mouse monocyte-macrophage cells after treatment of oxidative stress and endotoxin. The amount of Prx I, Prx II and Trx are increased in local inflammatory site but not increased in injured lung of septic animal model.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.7
• /
• pp.2979-2986
• /
• 2014

Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

• Proceedings of the Korean Society of Applied Entomolohy Conference
• /
• 2002.05a
• /
• pp.176-176
• /
• 2002

• Proceedings of the Korean Society of Sericultural Science Conference
• /
• 2002.04a
• /
• pp.66-66
• /
• 2002

No Abstract, See Full Text

• Proceedings of the Korean Society of Applied Entomolohy Conference
• /
• 2003.10a
• /
• pp.102-102
• /
• 2003

• Biomolecules & Therapeutics
• /
• v.18 no.3
• /
• pp.271-279
• /
• 2010

Streptococcus pneumoniae is the major pathogen that frequently causes serious infections in children, the elderly and immunocompromised patients. S. pneumoniae is known to produce reactive oxygen species (ROS) and S. pneumoniae-produced ROS is considered to play a role in pneumococci pathogenesis. SIGN-R1 is the principal receptor of capsular polysaccharides (CPSs) of S. pneumoniae. However, there is a considerable lack of knowledge about the protective role of SIGN-R1 against S. pneumoniae-produced ROS in SIGN-$R1^+$ macrophages. While investigating the protective role of SIGN-R1 against ROS, we found that SIGN-R1 intimately bound to peroxiredoxin-1 (Prx-1), one of small antioxidant proteins in vitro and in vivo. This interaction was increased with ROS generation which was produced by stimulating SIGN-R1 with dextran, a polysaccharide ligand of SIGN-R1. Also, SIGN-R1 crosslinking with 22D1 anti-SIGN-R1 antibody increased Prx-1 in vitro or in vivo. These results suggested that SIGN-R1 stimulation with CPSs of S. pneumoniae increase the expression level of Prx-1 through ROS and its subsequent interaction to SIGN-R1, providing an important antioxidant role for the host protection against S. pneumoniae.

• Applied Microscopy
• /
• v.35 no.4
• /
• pp.16-23
• /
• 2005

Peroxiredoxins (Prxs) are a superfamily of thiol-specific antioxidant proteins present in all organism and involved in the hydroperoxide detoxification of the cell. To determine the structural organization of yeast-Prx, electron microscopic analysis was performed. The average images of yeast-Prxs revealed three different structure, i.e. spherical-shaped structure, ring-shaped structure and irregularly-shaped small particles. In order to analyze the conformational change of yeast-Prx by reduction and oxidation, Prxs were subjected to DTT and $H_2O_2$. In presence of DTT, yeast-Prx showed a high tendency to form a decamer. However, they changed into dimeric or spherical structure in the oxidized state. Here we also show ionic interaction between dimeric subunits is primarily responsible for yeast-Prx oligomerization.

• Molecules and Cells
• /
• v.19 no.1
• /
• pp.39-45
• /
• 2005

RPK118 is a sphingosine kinase-1-binding protein that has been implicated in sphingosine 1 phosphate-mediated signaling. It contains a PX (phox homology) domain and two pseudo-kinase domains, and co-localizes with sphingosine kinase-1 on early endosomes. In this study we identified a novel RPK118-binding protein, PRDX3 (peroxiredoxin-3), by yeast two-hybrid screening. The interaction between these proteins was confirmed by pull-down assays and co-immunoprecipitation experiments. Deletion studies showed that RPK118 interacted with PRDX3 through its pseudokinase domains, and with early endosomes through its PX domain. Double immunofluorescence experiments demonstrated that PRDX3 co-localized with RPK118 on early endosomes in COS7 cells. PRDX3 is a member of the antioxidant family of proteins synthesized in the cytoplasm and functioning in mitochondria. Our findings indicate that RPK118 is a PRDX3-binding protein that may be involved in transporting PRDX3 from the cytoplasm to its mitochondrial site of function or to other membrane structures via endosome trafficking.