• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.402-407
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• 1996

Effects of oxidative stress on the induction of apoptosis and the activity of antioxidant enzymes were investigated in HL-60 cells using $H_2O$$_2$and cisplatin which generate oxygen species in the cell. Various concentrations of oxidants were treated to cells and at different incubation time, cells were harvested for assays. Cell viability, morphology by propidium iodide staining and DNA fragmentation by agarose gel electrophoresis were observed to determine whether they induce apoptosis. The activity of antioxidant enzymes such as superoxide dismutase and catalase was also measured to evaluate the cellular response to the oxidative damage. The results are as follows: $H_2O$$_2$ induced apoptosis at 10 $\mu$M after 6h incubation, while it took 12h for cisplatin. Both oxidants induced the superoxide dismutase activity at a tolerable low concentration. However, at a concentration which causes apoptotic cell death, the enzyme level was dropped markedly at first and then recovered to the normal level after which it declined again, probably due to cell death. On the other hand, changes in the activity of catalase were not significant at most concentrations except the statistically significant decrease at 24h after 10 $\mu$M-$H_2O$$_2$treatment. In this study, $H_2O$$_2$- and cisplatintreated cells showed similar results in apoptotic response and enzyme activities, suggesting that anticancer activity of cisplatin may be related, at least in part, to the production of oxygen free radicals.

• Archives of Pharmacal Research
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• v.29 no.1
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• pp.1-15
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• 2006

Vascular endothelial cell injury or dysfunction has been implicated in the onset and' progression of cardiovascular diseases including atherosclerosis. A number of previous studies have demonstrated that the pro-oxidative and pro-inflammatory pathways within vascular endothelium play an important role in the initiation and progression of atherosclerosis, Recent evidence has provided compelling evidence to indicate that interleukin-4 (IL-4) can induce proc inflammatory environment via oxidative stress-mediated up-regulation of inflammatory mediators such as cytokine, chemokine, and adhesion molecules in vascular endothelial cells. In addition, apoptotic cell death within vascular endothelium has been hypothesized to be involved in the development of atherosclerosis. Emerging evidence has demonstrated that IL-4 can induce apoptosis of human vascular endothelial cells through the caspase-3-dependent pathway, suggesting that IL-4 can increase endothelial cell turnover by accelerated apoptosis, the event which may cause the dysfunction of the vascular endothelium. These studies will have a high probability of revealing new directions that lead to the development of clinical strategies toward the prevention and/or treatment for individuals with inflammatory vascular diseases including atherosclerosis.

• Archives of Plastic Surgery
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• v.43 no.3
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• pp.237-241
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• 2016

Background Adipose-derived stem cells (ASCs) have applications in regenerative medicine based on their therapeutic potential to repair and regenerate diseased and damaged tissue. They are commonly subject to oxidative stress during harvest and transplantation, which has detrimental effects on their subsequent viability. By functioning as an antioxidant against free radicals, melatonin may exert cytoprotective effects on ASCs. Methods We cultured human ASCs in the presence of varying dosages of hydrogen peroxide and/or melatonin for a period of 3 hours. Cell viability and apoptosis were determined with propidium iodide and Hoechst 33342 staining under fluorescence microscopy. Results Hydrogen peroxide (1-2.5 mM) treatment resulted in an incremental increase in cell death. 2 mM hydrogen peroxide was thereafter selected as the dose for co-treatment with melatonin. Melatonin alone had no adverse effects on ASCs. Co-treatment of ASCs with melatonin in the presence of hydrogen peroxide protected ASCs from cell death in a dose-dependent manner, and afforded maximal protection at $100{\mu}M$ (n=4, one-way analysis of variance P<0.001). Melatonin co-treated ASCs displayed significantly fewer apoptotic cells, as demonstrated by condensed and fragmented nuclei under fluorescence microscopy. Conclusions Melatonin possesses cytoprotective properties against oxidative stress in human ASCs and might be a useful adjunct in fat grafting and cell-assisted lipotransfer.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.86-93
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• 1997

Even though both N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine have been widely used to establish the experimental model for dopaminergic neuronal ce ll death. mechanisms underlying this phenomenon have not been firmly explored. To investigate how these dopaminergic neurotoxins induce neuronal cell death, murine dopaminergic neuronal cell line, MN9D cells were treated with various concentration of either 6-hydroxydopamine or active form of MPTP, N methyl-4-phenylpyridinium (MPP$^+$). Treatment of cells with 5-100 uM 6-hydroxydopamine resulted in apoptotic cell death whereas cell death induced by 5~50 uM MPP$^+$ was not demonstrated typical apoptotic characteristics such as cell shrinkage, apoptotic body and nuclear condensation. Cell death induced by 6-hydroxydopamine was partially blocked in the presence of antioxidants including soluble form of vitamin E or desferrioxamine suggesting that generation of oxidative stress may be associated with 6-hydroxydopamine-induced cell death in MN9D cells. In contrast, MPP$^+$-induced cell death was not blocked by treatment with any of antioxidants tested. As previously demonstrated that MPP$^+$ caused metabolic alterations such as glucose metabolism, removal of glucose from the medium partially inhibited MPP$^+$-induced cell death suggesting excessive cycles of glycolysis may be associated with MPP$^+$-induced cell death. Taken together, these studies demonstrate that two types of dopaminergic neurotoxins recruit distinct neuronal cell death pathways.

• Molecules and Cells
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• v.43 no.3
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• pp.264-275
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• 2020

Reactive oxygen species (ROS) play a significant role in intracellular signaling and regulation, particularly when they are maintained at physiologic levels. However, excess ROS can cause cell damage and induce cell death. We recently reported that eIF2α phosphorylation protects hepatocytes from oxidative stress and liver fibrosis induced by fructose metabolism. Here, we found that hepatocyte-specific eIF2α phosphorylation-deficient mice have significantly reduced expression of the epidermal growth factor receptor (EGFR) and altered EGFR-mediated signaling pathways. EGFR-mediated signaling pathways are important for cell proliferation, differentiation, and survival in many tissues and cell types. Therefore, we studied whether the reduced amount of EGFR is responsible for the eIF2α phosphorylation-deficient hepatocytes' vulnerability to oxidative stress. ROS such as hydrogen peroxide and superoxides induce both EGFR tyrosine phosphorylation and eIF2α phosphorylation. eIF2α phosphorylation-deficient primary hepatocytes, or EGFR knockdown cells, have decreased ROS scavenging ability compared to normal cells. Therefore, these cells are particularly susceptible to oxidative stress. However, overexpression of EGFR in these eIF2α phosphorylation-deficient primary hepatocytes increased ROS scavenging ability and alleviated ROS-mediated cell death. Therefore, we hypothesize that the reduced EGFR level in eIF2α phosphorylation-deficient hepatocytes is one of critical factors responsible for their susceptibility to oxidative stress.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.48-64
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• 2002

The primary recognized health risk from common deficiencies in glucose-6-phosphate dehydrogenase (G6PD), a cytoprotective enzyme for oxidative stress, is red blood cell hemolysis. Here we show that litters from untreated pregnant mutant mice with a hereditary G6PD deficiency had increased prenatal (fetal resorptions) and postnatal death. When treated with the anticonvulsant drug phenytoin, a human teratogen that is commonly used in pregnant women and causes embryonic oxidative stress, G6PD-deficient dams had higher embryonic DNA oxidation and more fetal death and birth defects. The reported G6PD gene mutation was confirmed and used to genotype fetal resorptions, which were primarily G6PD deficient. This is the first evidence that G6PD is a developmentally critical cytoprotective enzyme for both endogenous and xenobiotic-initiated embryopathic oxidative stress and DNA damage. G6PD deficiencies accordingly may have a broader biological relevance as important determinants of infertility, in utero and postnatal death, and teratogenesis.-Nicol, C. J., Zielenski, J., Tsui, L.-C., Wells, P. G. An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis.

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.730-732
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• 2003

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.207.1-207.1
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• 2000

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.101.1-101.1
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• 2002

• Journal of Oriental Neuropsychiatry
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• v.20 no.2
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• pp.19-29
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• 2009

Objectives : Antioxidant effects of Gagam-jangwonhwan(LMK01 and 02) water extract against $H_2O_2$-induced oxidative damage and cell death were investigated in rat pheochromocytoma line PC 12. Methods : The cells were treated with LMK01 and 02 water extract and $H_2O_2$, oxidative damage-inducing materials for 24 h. The cellular viability was assessed by WST-1 assay, oxidative damages of the cells by 8-OHdG quantitation, apoptosis by Hoechst 33342 staining assay and activity of antioxidant enzymes by catalase and glutathione peroxidase assay. Results : 1. LMK01 and LMK02 water extracts improved significantly cell viability in $H_2O_2$-treated groups than $H_2O_2$-alone treated cells 2, LMK02 suppressed significantly oxidative damage in $H_2O_2$-treated groups than $H_2O_2$-alone treated cells but LMK01 didn't. Meanwhile, difference of oxidative damages in conditions treated with LMK01 or LMK02 was not significant, 3. The $H_2O_2$ induced-apoptosis in PC 12 cell lines was inhibited effectively by LMK01 and LMK02, and especially the features of apoptosis were obviously reduced in LMK02-treated cells. 4. LMK01 and LMK02 increased significantly activities of both catalase and glutathione peroxidase than those of $H_2O_2$-alone treated group and moreover, LMK02 showed significantly higher activities than those of LMK01. Conclusions : As shown, LMK01 and LMK02 suppressed $H_2O_2$-induced oxidative damage and cell death in PC 12 cell effectively. And they increased activity of major antioxidant enzymes in PC 12 cell line. Therefore, this study suggests the possibility of clinical usage over oxidative stress-induced neurodegenerative disease such as Alzheimer's disease.