• 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.

• Molecules and Cells
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• v.39 no.3
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• pp.266-279
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• 2016

The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) ${\alpha}$ and $PKC{\beta}1$ exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. $PKC{\alpha}$ accompanied pErk1/2 to the nucleus after freeing it from $PEA-15pS^{104}$ via $PKC{\beta}1$ and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of $PKC{\alpha}$ were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated $PKC{\alpha}$ expression and increased epidermal and hair follicle cell proliferation. Thus, $PKC{\alpha}$ downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear $PKC{\alpha}$ degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of $PKC{\alpha}$ expression following TPA treatment reduces pErk1/2-activated SP1 biding to the $p21^{WAF1}$ gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.

• Preventive Nutrition and Food Science
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• v.12 no.4
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• pp.202-208
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• 2007

Persimmon is well-known as a Korean traditional medicine for alleviating coughs and enhancing blood circulation; it is also used for treatment of hypertension, cancer, diabetes and atherosclerosis. To evaluate the protective properties of persimmon leaf methanol extract (PLME) and persimmon fruit methanol extract (PFME) administration on acute ethanol-induced hepatotoxicity, C57BL/6 male mice were gavaged with or without persimmon extracts for 1 week. Hepatotoxicity was then induced by gavage of 5 g/kg BW ethanol. After 12 hr of ethanol administration, blood and liver were collected and analyzed for biochemical markers of hepatotoxicity. The results showed PLME and PFME treatments decreased the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with ethanol control. Both PLME and PFME reduced serum lactate dehydrogenase (LDH) activity, but elevated alcohol dehydrogenase (ADH) activity. Serum triglyceride (TG) and hepatic cholesterol levels were significantly decreased when treated with PLME and PFME. Liver malondialdehyde (MDA) levels were significantly decreased in PLME and PFME groups compared with ethanol control. Furthermore, the administration of PLME and PFME significantly increased the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-red). In summary, PLME and PFME appeared to prevent hepatic injury by accelerating alcohol metabolism by increasing alcohol-metabolizing enzyme activities, by activating the antioxidative enzyme system against oxidative stress, and by decreasing fat accumulation, which is evidenced by decreased hepatotoxic indices in serum.

• Journal of Preventive Medicine and Public Health
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• v.27 no.3 s.47
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• pp.569-579
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• 1994

The genetically determined ability to metabolize debrisoquine (DBR) is related to risk of lung cancer and DBR hydroxylation exhibits wide inter-individual variation. In this study, 100 korean adults were tested for their ability to metabolize DBR. The DBR metabolic phenotype were determined by metabolic ratio (MR, DBR / 4-HDBR) which is the percent dose excreted as unchanged DBR divided by the percent dose excreted as 4-hydroxyebrisoquine(4-HDBR) in a aliquot of an eight hour urine sample, after 10mg DBR test dose administration. Analysis was performed on a capillary gas chromatograph fitted with electron capture detector. The results were as follows; 1 Geometric mean of DBR MR was 0.32 in male,0.27 in female,0.30 in total and the distribution of log (MR) was seemed to follow normal distribution. 2. Metabolic ratio of DBR was higher in non-smoker and non-drinker than in smoker and drinker without any statistically significant difference. 3. None of personal factors was significantly related to DBR MR except age. 4. The DBR metabolic phenotype was extensive metabolizer(EM) 93, intermediate metabolizer(IM) 7 by traditional method and EM 98, IM 3 by Caporaso's method. The poor metabolizer (PM) phenotype was not found by either method. 5. Maximal expected PM phenotype was 0.36% by traditional method and 0.04% by Caporaso's method.

• Journal of Pharmacopuncture
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• v.10 no.2 s.23
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• pp.25-30
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• 2007

Objectives : Free radical metabolism seems to occupy a remarkably common position in the mechanisms of aging and aging related disease. Oxidative damage to DNA, lipids. proteins and other molecules may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. This study was designed to find out whether Carthami Flos Herbal-Acupuncture Solution can scavenge Nitric Oxide(NO) or not. SNAP is NO generator. NO concentration was estimated after 2,6, 12 and 24 hrs in no treatment group, after treatment with Vit. C or 1, 10, 100${\mu}$g/m1 of Carthami Flos Herbal-Acupuncture Solution. There was no significant scavenging effect of Carthami Flos Herbal-Acupuncture Solutionon NO after 2 hrs. But there was a significant scavenging effect of Cafhami Flos Herbal-Acupuncture Solution on NO in 10${\mu}$/m1 group after 6hrs. And there was a significant scavenging effect of carthami Flos Herbal-Acupuncture Solution on NO in 1, 10${\mu}$g/ml group after 12, 24 hrs. These results suggest that Carhami Flos Herbal-Acupuncture Solution has scavenging effect on NO. This study shows that Carthami Flos Herbal-Acupuncture Solution can be used for aging related disease and further studies are required to investigate the antioxidative effects of it.

• Molecules and Cells
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• v.43 no.1
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• pp.86-95
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• 2020

The red-crowned crane (Grus japonensis) is an endangered, large-bodied crane native to East Asia. It is a traditional symbol of longevity and its long lifespan has been confirmed both in captivity and in the wild. Lifespan in birds is known to be positively correlated with body size and negatively correlated with metabolic rate, though the genetic mechanisms for the red-crowned crane's long lifespan have not previously been investigated. Using whole genome sequencing and comparative evolutionary analyses against the grey-crowned crane and other avian genomes, including the long-lived common ostrich, we identified redcrowned crane candidate genes with known associations with longevity. Among these are positively selected genes in metabolism and immunity pathways (NDUFA5, NDUFA8, NUDT12, SOD3, CTH, RPA1, PHAX, HNMT, HS2ST1, PPCDC, PSTK CD8B, GP9, IL-9R, and PTPRC). Our analyses provide genetic evidence for low metabolic rate and longevity, accompanied by possible convergent adaptation signatures among distantly related large and long-lived birds. Finally, we identified low genetic diversity in the red-crowned crane, consistent with its listing as an endangered species, and this genome should provide a useful genetic resource for future conservation studies of this rare and iconic species.

• Mass Spectrometry Letters
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• v.9 no.1
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• pp.24-29
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• 2018

DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

• Journal of Nutrition and Health
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• v.31 no.7
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• pp.1121-1129
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• 1998

The critical role of folate vitamin in the remethylation pathway for methionine synthesis from homocysteine has been well documented. Hyperhomocysteinemia resulting from inadequate folate nutrition has been implicated in increased incidence of macrovascular diseases, colorectal cancer, neural tube defects, etc. Chronic exposure to ethanol impairs folate nutrition and one-carbon metabolism in the liver, which often results in fatty liver due to a defective remethylation process. This study was carried out to investigate the chronic effects of moderate levels of alcohol and dietary 131ate on plasma homocysteine levels, and on histopathology and biochemical functions of the liver Rats were raised on experimental diets with three levels of folate(0, 2, 8mg/kg diet), and 50% ethanol(1.8m1/kg body weight) was administered intragastrically by intubation tubes three times a week for 10 weeks. Plasma homocysteine concentrations were found to be significantly influenced by dietary folate intake and alcohol administration. Among all treatment groups, Plasma homocysteine levels were highest in the animals receiving a combined treatment of folate deficient diet and alcohol administration. Plasma homocysteine concentration was negatively correlated with folate concentration in the plasma(p<0.01) and liver(p<0.05). Among alcohol treated rats, increase in plasma homocysteine values due to ethanol was prevented by 131ate supplementation. When liver histological tests were performed, macrovascular and microvascular fatty changes and spotted necrosis were observed more frequently in folate-deficient animals diet than those on folate-adequate and folate-supplemented diets in alcohol-treated rats. These results indicate that folate supplementation above the recommended level might be beneficial in the prevention of alcohol-related hyperhomocystei-nemia and abnormal histologic changes in the liver due. (Korean J Nutrition 31(7) : l121-l129, 1998)

• Clinical and Experimental Reproductive Medicine
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• v.48 no.3
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• pp.236-244
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• 2021

Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, irregular menstruation, ovulatory dysfunction, and insulin resistance. Recent studies have reported the possible role of phytoestrogens in PCOS. This animal study aimed to evaluate the effects of genistein on insulin resistance, inflammatory factors, lipid profile, and histopathologic indices on PCOS. Methods: PCOS was induced by 1 mg/kg of letrozole in adult Sprague-Dawley rats. The rats then received normal saline (PCOS group), 150 mg/kg of metformin, or 20 mg/kg of genistein dissolved in 1% methylcellulose solution for 42 days. Body weight, the glycemic and lipid profile, and inflammatory, antioxidative, and histopathological parameters were assessed at the end of the intervention. Results: Treatment with genistein significantly alleviated the increased level of fasting blood insulin (p=0.16) and the homeostatic model assessment of insulin resistance (p=0.012). In addition, the genistein group had significantly lower levels of serum malondialdehyde (p=0.039) and tumor necrosis factor-alpha (p=0.003), and higher superoxide dismutase enzyme activity (p<0.001). Furthermore, the histopathological analysis indicated that genistein administration led to an increase in luteinization and the development of fewer cysts (p<0.05). Conclusion: Biochemical and histopathological analyses indicated that genistein administration to rats with PCOS induced significant remission in oxidative, inflammatory, and glycemic and histopathologic parameters.

• Nutrition Research and Practice
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• v.16 no.1
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• pp.46-59
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• 2022

BACKGROUND/OBJECTIVES: Aster yomena (Kitam.) Honda (AY) has remarkable bioactivities, such as antioxidant, anti-inflammation, and anti-cancer activities. On the other hand, the effects of AY against obesity-induced insulin resistance have not been reported. Therefore, this study examined the potential of AY against obesity-associated insulin resistance in high-fat diet (HFD)-fed mice. MATERIALS/METHODS: An obesity model was established by feeding C57BL/6J mice a 60% HFD for 16 weeks. The C57BL6/When ethyl acetate fraction from AY (EFAY) at doses of 100 and 200 mg/kg/day was administered orally to mice fed a HFD for the last 4 weeks. Normal and control groups were administered water orally. The body weight and fasting blood glucose were measured every week. Dietary intake was measured every other day. After dissection, blood and tissues were collected from the mice. RESULTS: The administration of EFAY reduced body and organ weights significantly compared to HFD-fed control mice. The EFAY-administered groups also improved the serum lipid profile by decreasing the triglyceride, total cholesterol, and low-density lipoprotein compared to the control group. In addition, EFAY ameliorated the insulin resistance-related metabolic dysfunctions, including the fasting blood glucose and serum insulin level, compared to the HFD-fed control mice. The EFAY inhibited lipid synthesis and insulin resistance by down-regulation of hepatic fatty acid synthase and up-regulation of the AMP-activated protein kinase pathway. EFAY also reduced lipid peroxidation in the liver, indicating that EFAY protected hepatic injury induced by obesity. CONCLUSIONS: These results suggest that EFAY improved obesity-associated insulin resistance by regulating the lipid and glucose metabolism, suggesting that AY could be used as a functional food to prevent obesity and insulin resistance.