• Molecules and Cells
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• v.27 no.3
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• pp.279-282
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• 2009

"Two-cysteine" peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin's role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here, the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress.

• Molecules and Cells
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• v.43 no.9
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• pp.813-820
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• 2020

NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2', 7'-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX™ Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO₂ (Cysteine sulfinic acid, Cys-SO₂H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO₂ form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.

• The Korean Journal of Food And Nutrition
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• v.4 no.1
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• pp.21-34
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• 1991

The purposes of this studies were to investigate the effect of dietry Se levels and alcohol administration on the lipid hyperoxidation and the lipid metabolism in the rat. Seventy two male rats of Sprague-Dawley Strain weighting about 58~629 were divided into 12groups. The dietary Se levels were 10, 0.4 and Omg, and the dietary a-tocopherol levels were 150 and 0mg per kg diet, respectively. Alcohol-administrated groups received drinking water solution containing 10% of ethanol from the 3-weeks of experimental periods. The obtained experimental results are summarized as follows. 1. Food intake, body weight gain and food efficiency ratio were significantly lower in H-, L-and alcohol administrated groups(-A) by administrated Se and alcohol in diet. The weight of liver and spleen tended to be greater in H- and alcohol administrated groups. 2. The glutathione values in liver tend to be lower in alcohol or Vit. E administrated groups than nonadministrated groups. Also there were higher in H- and L- than C-groups, but the increasing range decreased due to administrated alcohol. The lipid peroxide values In liver were significantly higher in alcohol groups, and L- and tocopherol groups were higher values. Specially the increasing of lipid peroxide values were significantly effected by alcohol in low Se and Vit. E groups. 3. The contents of total glyceride in plasma were higher in alcohol groups, there were significantly higher values in alcohol administrated groups under low Se and Vit. E groups. The contents of total cholesterol and HDL-cholesterol In plasma were significantly higher in alcohol groups. 4. The contents of total lipid in liver were higher alcohol groups, and slightly higher values in low Se groups(L-groups) than other groups, also higher values in low Vit. E groups. Those of total glyceride in liver were significantly higher in alcohol groups, appeared highest values when alcohol was administrated in low Se and Vit. E groups. The increasing of total glyceride content was significantly effected by alcohol in low Se groups than that in C-groups.

• Molecules and Cells
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• v.39 no.1
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• pp.26-30
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• 2016

Peroxiredoxins are ubiquitous thiol proteins that catalyse the breakdown of peroxides and regulate redox activity in the cell. Kinetic analysis of their reactions is required in order to identify substrate preferences, to understand how molecular structure affects activity and to establish their physiological functions. Various approaches can be taken, including the measurement of rates of individual steps in the reaction pathway by stopped flow or competitive kinetics, classical enzymatic analysis and measurement of peroxidase activity. Each methodology has its strengths and they can often give complementary information. However, it is important to understand the experimental conditions of the assay so as to interpret correctly what parameter is being measured. This brief review discusses different kinetic approaches and the information that can be obtained from them.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.2
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• pp.116-126
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• 1993

The purposes of this study were to investigate the effect of seleniumc (Se) and vitamin E on activity of enzyme relevant to lipid peroxidation in alcohol administrated rats. Seventy two male rats of Sprague-Dawley strain weighing about 58~62g were divided into 12groups. The dietary Se levels were 0, 0.4 and 10mg and the dietary vitamin E levels were 0 and 150mg per kg diet, respectively. Alcohol-administrated groups received drinking water solution containing 10% of ethanol from the 3-weeks of experimental periods. The obtained experimental results are summarized as follow: The ${\gamma}$-GTP activity in plasma was higher in alcohol administrated groups and high selenium group (HSe) and low selenium group (LSe) than in control groups (CSe). The ${\gamma}$-GOT and GPT activities were higher in alcohol groups. The ${\gamma}$-GTP activity was significantly influenced by alcohol in LSe groups than in other groups. The glutathione peroxidase (GSH-Px) activity of plasma was significantly lower in LSe groups than HSe and CSe groups. The GSH-Px activity of microsomal and cytosolic fraction was slightly lower in alcohol groups and was about a half value lower in HSe and LSe groups than CSe groups. There was negative correlation between plasma Se level and GSH-Px activity of cytosolic fraction in HSe groups (r=- 0.662, p<0.001) and positive correlation in LSe groups (r=0.640, p<0.001). The GSH S-transferase activity in microsomal and cytosolic fraction was slightly higher in alcohol administrated but vitamin E nonadministrated groups, and significantly higher in LSe groups than in other groups. The catalase activity in mitochondria was lower in HSe than CSe groups, but rather higher in LSe groups. The superoxide dismutase (SOD) activity in cytosolic fraction of liver was not found any effect in all groups. The cytochrome P-450 was higher in alcohol groups, but significantly lower in HSe groups. In conclusion, the deficiency of Se and vitamin E develops the hyperoxidation of liver lipid through the increase of activity of enzyme related to the lipid peroxidation and alcohol administration appears to further increase of hyperoxidation of liver lipid.

• Journal of Plant Biotechnology
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• v.33 no.1
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• pp.1-9
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• 2006

Peroxiredoxins (Prxs) are ubiquitously distributed and play important functions in diverse cellular signaling systems. The proteins are largely classified into three groups, such as typical 2-Cys Prx, atypical 2-Cys Prx, and 1-Cys Prx, that are distinguished by their catalytic mechanisms and number of Cys residues. From the three classes of Prxs, the typical 2-Cys Prx containing the two-conserved Cys residues at its N-terminus and C-terminus catalyzes $H_2O_2$ with the use of thioredoxin (Trx) as an electron donor. During the catalytic cycle, the N-terminal Cys residue undergoes a peroxide-dependent oxidation to sulfenic acid, which can be further oxidized to sulfinic acid at the presence of high concentrations of $H_2O_2$ and a Trx system containing Trx, Trx reductase, and NADPH. The sulfinic acid form of 2-Cys Prx is reduced by the action of sulfiredoxin which requires ATP as an energy source. Under the strong oxidative or heat shock stress conditions, 2-Cys Prx in eukaryotes rapidly switches its protein structure from low-molecular-weight species to high-molecular-weight protein structures. In accordance with its structural changes, the protein concomitantly triggers functional switching from a peroxidase to a molecular chaperone, which can protect its substrate denaturation from external stress. In addition to its N-terminal active site, the C-terminal domain including 'YF-motif' of 2-Cys Prx plays a critical role in the structural changes. Therefore, the C-terminal truncated 2-Cys Prxs are not able to regulate their protein structures and highly resistant to $H_2O_2$-dependent hyperoxidation, suggesting that the reaction is guided by the peroxidatic Cys residue. Based on the results, it may be concluded that the peroxidatic Cys of 2-Cys Prx acts as an '$H_2O_2$-sensor' in the cells. The oxidative stress-dependent regulation of 2-Cys Prx provides a means of defense systems in cells to adapt stress conditions by activating intracellular defense signaling pathways. Particularly, 2-Cys Prxs in plants are localized in chloroplasts with a dynamic protein structure. The protein undergoes conformational changes again oxidative stress. Depending on a redox-potential of the chloroplasts, the plant 2-Cys Prx forms super-molecular weight protein structures, which attach to the thylakoid membranes in a reversible manner.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.10
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• pp.1336-1342
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• 2006

This study was performed to investigate the effect of ethanol extract of Chaenomeles sinensis Koehne (CS) on alcohol-induced liver damage in rats. Male Sprague-Dawley rats weighing $135{\pm}10g$ were divided into 6 groups for 4 weeks; normal group (ND), alcohol (35%, 10 mL/kg/day) treated group (ET), CS ethanol extract 200 mg/kg/day treated group (ND-CSL), CS ethanol extract 400 mg/kg/day treated group (ND-CSH), CS ethanol extract 200 mg/kg/day and alcohol treated group (ET-CSL), and CS ethanol extract 400 mg/kg/day and alcohol treated group (ET-CSH). The body weight gain and food efficiency ratio were no differences between ND and ET. There were increases in the activities of serum alanine aminotransferase (ALT), asparate aminotransferase (AST), and alkaline phosphatase (ALP) in ET. On the other hand, the administration of CS decreased ALT, AST and ALP activities in serum. It was also observed that the hepatic activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) increased by alcohol treatment were also markedly decreased in the CS administered groups as compared with ET. The activities of hepatic SOD, catalase, GSH-Px and XO were riot significantly different among the normal diet groups. Contents of thiobarbituric acid reactive substances (TBARS) were increased by the administration of alcohol, on the other hand, the administration of CS reduced TBARS value in the liver. In addition, the content of glutathione (GSH) in the liver was decreased by alcohol administration, however, GSH increased after administering CS. In conclusion, the administration of alcohol develops the hyperoxidation of liver lipids through tile increase in enzymes activity related to the lipid peroxiation, however, it was decreased after administring CS. Thus, CS may have a possible protective effect on ethanol-induced hepatotoxicity in rat liver.