• International Journal of Industrial Entomology and Biomaterials
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• v.47 no.2
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• pp.134-139
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• 2023

SIRT5 and PRDx1 play crucial roles in cancer and are involved in the basic mechanisms of reactive oxygen species detoxification. In our previous studies, we showed that hemolymph extracts of immune-challenged Bombyx mori have antioxidant properties. Following H₂O₂ stimulation, immune-challenged B. mori hemolymph extracts elicited SIRT5 downregulation activity, reaching effective activity at the highest concentration of 100 ppm. Additionally, cells treated with immune-challenged B. mori hemolymph extracts demonstrated increased PRDx1 mRNA expression compared to that of PBS-treated cells. Therefore, immune-challenged B. mori hemolymph extracts offer a potential auxiliary means of treating drug-resistant tumors through downregulation of SIRT5 and upregulation of PRDx1 expression. Nevertheless, further studies on the effects of B. mori hemolymph on SIRT5 and PRDx1 regulation are pertinent for using it as a food or pharmaceutical material and understanding its therapeutic effect on tumors, including those that are drug-resistant.

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

• Reproductive and Developmental Biology
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• v.36 no.1
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• pp.55-64
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• 2012

Peroxiredoxin II (Prdx II; a typical 2-Cys Prdx) has been originally isolated from erythrocytes, and its structure and peroxidase activity have been adequately studied. Prdx II has been reported to protect a wide range of cellular environments as antioxidant enzyme, and its dysfunctions may be implicated in a variety of disease states associated with oxidative stress, including cancer and aging-associated pathologies. But, the precise mechanism is still obscure in various aspects of aging containing ovarian aging. Identification and relative quantification of the increased proteins affected by Prdx II deficiency may help identify novel signaling mechanisms that are important for oxidative stress-related diseases. To identify the increased proteins in Prdx $II^{-/-}$ mice, we performed RBC comparative proteome analysis in membrane fraction and cytosolic fractions by nano-UPLC-$MS^E$ shotgun proteomics. We found the increased 86 proteins in membrane (32 proteins) and cytosolic (54 proteins) fractions, and analyzed comparative expression pattern in healthy RBCs of Prdx $II^{+/+}$ mice, healthy RBCs of Prdx $II^{-/-}$ mice, and abnormal RBCs of Prdx $II^{-/-}$ mice. These proteins belonged to cellular functions related with RBC lifespan maintain, such as cellular morphology and assembly, cell-cell interaction, metabolism, and stress-induced signaling. Moreover, protein networks among the increased proteins were analyzed to associate with various diseases. Taken together, RBC proteome may provide clues to understand the clue about redox-imbalanced diseases.

• Clinical and Experimental Pediatrics
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• v.56 no.3
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• pp.107-111
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• 2013

Preterm infants are vulnerable to the oxidative stress due to the production of large amounts of free radicals, antioxidant system insufficiency, and immature oligodendroglial cells. Reactive oxygen species (ROS) play a pivotal role in the development of periventricular leukomalacia. The three most common ROS are superoxide ($O2^{\cdot-}$), hydroxyl radical ($OH^{\cdot}$), and hydrogen peroxide ($H_2O_2$). Under normal physiological conditions, a balance is maintained between the production of ROS and the capacity of the antioxidant enzyme system. However, if this balance breaks down, ROS can exert toxic effects. Superoxide dismutase, glutathione peroxidase, and catalase are considered the classical antioxidant enzymes. A recently discovered antioxidant enzyme family, peroxiredoxin (Prdx), is also an important scavenger of free radicals. Prdx1 expression is induced at birth, whereas Prdx2 is constitutively expressed, and Prdx6 expression is consistent with the classical antioxidant enzymes. Several antioxidant substances have been studied as potential therapeutic agents; however, further preclinical and clinical studies are required before allowing clinical application.

• BMB Reports
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• v.48 no.10
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• pp.539-540
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• 2015

It has been proposed that the selective elimination of cancer stem cells (CSCs) using targeted therapy could greatly reduce tumor growth, recurrence, and metastasis. To develop effective therapeutic targets for CSC elimination, we aimed to define the properties of CSC mitochondria, and identify CSC-mitochondria-specific targets in colon cancer. We found that colon CSCs utilize mitochondrial oxidative phosphorylation (OXPHOS) to produce ATP. We also found that forkhead box protein 1 (FOXM1)-induced peroxiredoxin 3 (PRDX3) maintains the mitochondrial function, and the FOXM1/PRDX3 mitochondrial pathway maintains survival of colon CSCs. Furthermore, FOXM1 induces CD133 (PROM1/prominin 1) expression, which maintains the stemness of colon CSCs. Together, our findings indicate that FOXM1, PRDX3, and CD133 are potential therapeutic targets for the elimination of CSCs in colon cancer.

• International Journal of Oral Biology
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• v.34 no.4
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• pp.205-213
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• 2009

The mechanisms underlying the actions of the antioxidants upon reactive oxygen species (ROS) generation by NADPH oxidase complex have remained uncertain. In this study, we investigated NADPH oxidase activity and the role of antioxidant enzymes upon the generation of ROS during hypoxic stress. ROS generation was found to increase in the mouse kidney under hypoxic stress in a time-dependent manner. Moreover, we found in MCT cells that hypoxia-induced hydrogen peroxide production was decreased by NAC pretreatment. We further analyzed HIF-$1{\alpha}$, PHD2 and VHL expression in the NAC-pretreated MCT cells and assessed the response of antioxidant enzymes at the transcriptional and translational levels. SOD3 and Prdx2 were significantly increased during hypoxia in the mouse kidney. We also confirmed in hypoxic $Prdx2^{-/-}$ and SOD3 transgenic mice that erythropoietin (EPO) is transcriptionally regulated by HIF-$1{\alpha}$. In addition, although EPO protein was found to be expressed in a HIF-$1{\alpha}$ independent manner in three mouse lines, its activity differed markedly between normal and $Prdx2^{-/-}$/SOD3 transgenic mice during hypoxic stress. In conclusion, our current results indicate that NADPH oxidase-mediated ROS generation is associated with hypoxic stress in the mouse kidney and that SOD3 and Prdx2 cooperate to regulate cellular redox reactions during hypoxia.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.50-57
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• 2020

Background: The cellular senescence of primary cultured cells is an irreversible process characterized by growth arrest. Restoration of senescence by ginsenosides has not been explored so far. Rg3(S) treatment markedly decreased senescence-associated β-galactosidase activity and intracellular reactive oxygen species levels in senescent human dermal fibroblasts (HDFs). However, the underlying mechanism of this effect of Rg3(S) on the senescent HDFs remains unknown. Methods: We performed a label-free quantitative proteomics to identify the altered proteins in Rg3(S)-treated senescent HDFs. Upregulated proteins induced by Rg3(S) were validated by real-time polymerase chain reaction and immunoblot analyses. Results: Finally, 157 human proteins were identified, and variable peroxiredoxin (PRDX) isotypes were highly implicated by network analyses. Among them, the mitochondrial PRDX3 was transcriptionally and translationally increased in response to Rg3(S) treatment in senescent HDFs in a time-dependent manner. Conclusion: Our proteomic approach provides insights into the partial reversing effect of Rg3 on senescent HDFs through induction of antioxidant enzymes, particularly PRDX3.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.1
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• pp.1-12
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• 2020

Objectives Depletion of ovarian function after menopause in women induces estrogen deficiency leading to increased fat and decreased muscle mass. In this study, we examined the effect of herbal medicines by measuring hormone expression in muscle tissue of estrogen-deficient rats induced by ovariectomy. Methods Ovariectomy was performed to induce estrogen deficiency, and mice were given herbal prescription (HP) for 6 weeks. Estrogen-deficient rats were divided into two groups: one group (HPH) which were orally administered HP 200 mg/kg and the other group (HPL) administered HP 40 mg/kg. Weight changes in both groups were measured using polymerase chain reaction (PCR). After extraction of the femoral muscles in mice, the expression of the leptin, lipoprotein lipase (LPL), diacyl glycerol acyltransferase (DGAT)1, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, NADH dehydrogenase (NDH), farnesyl diphosphate farnesyltransferase (FDFT)1, lanosterol synthase (LSS), phosphatidylethanolamine N-methyltransferase (PEMT), and peroxiredoxin (Prdx6) were measured using PCR. Results HP increased the expression of leptin, LPL, DGAT1, PGC-1α, NDH, FDFT1, LSS, PEMT, and Prdx6. HP affects body fat metabolism and is effective in improving menopausal obesity and obesity complications caused by estrogen deficiency. However, HP does not affect the expression of tumor necrosis factor-α and 3-hydroxy-3-methylglutaryl-CoA reductase, and thus will not be effective in obesity-related metabolic diseases. Conclusions HP is thought to inhibit weight gain by regulating hormone expression related to glucose metabolism and lipid metabolism in muscle tissue of estrogen-deficient rats.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.277-286
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• 2016

Makgeolli lees (ML) has several physiological effects such as antioxidant, antidiabetic, and anticancer properties, but its biological functions have not been determined definitively. Here, we tested whether ML has a cytoprotective effect on paraquat (PQ)-induced oxidative stress in the human lung carcinoma cell line A549. At 0.1 mg/ml ML, viability of PQ-exposed A549 cells was restored by 12.4%, 18.5%, and 48.6% after 24, 48, and 72 h, respectively. ML also reduced production of the intracellular reactive oxygen species (ROS) that were generated by PQ treatment. Further experiments revealed that ML treatment enhanced the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) as well as ARE-GFP reporter activity. ML treatment also effectively increased the expression of NRF2's target genes NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase 1 (HO-1). Moreover, we found that expression of cytoprotective genes, including glutathione peroxidases (GPXs), superoxide dismutase (SOD1), catalase (CAT), peroxiredoxin 3 (PRDX3), and peroxiredoxin 4 (PRDX4), was greatly enhanced by treatment with ML during PQ exposure. Taken together, the data suggest that treatment of PQ-exposed A549 cells with ML ameliorates cytotoxicity through induction of NRF2 expression and its target genes HO-1, NQO1, and other antioxidant genes. Thus, ML may serve as a functional food applicable to ROS-mediated human diseases.

• Biomedical Science Letters
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• v.18 no.1
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• pp.1-9
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• 2012

Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.