• BMB Reports
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• v.43 no.1
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• pp.57-61
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• 2010

Activator protein-1 can induce either cell survival or death, which is controlled by opposing effects of different Jun members. It is generally accepted that c-Jun is pro-apoptotic, but that JunD is anti-apoptotic in stress-exposed cells. Additionally, although there are reports suggesting that JunB plays a protective role, its role in stress-induced apoptosis remains unclear. Here, we investigated the role of JunB in $H_2O_2$-induced cell death using cells that over-expressed the protein or were transfected with si-JunB. Inhibition of JunB expression accelerated $H_2O_2$-mediated loss of mitochondrial membrane potential (MMP) and cytotoxicity. Conversely, over-expression of JunB protein led to significant inhibition of the MMP loss and cell death. The increase in JunB expression also attenuated nuclear relocation of apoptosis-inducing factor and mitochondrial Bcl-2 reduction that occurred following $H_2O_2$ exposure. These results suggest that JunB can signal survival against oxidant-mediated cell death by suppressing mitochondrial stress.

• Fisheries and Aquatic Sciences
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• v.26 no.1
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• pp.35-47
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• 2023

Myelophycus caespitosus, a brown alga belonging to genus Myelophycus, has been traditionally used as a food and medicinal resource in Northeastern Asia. However, few studies have been conducted on its pharmacological activity. In this study, we evaluated whether methanol extract of M. caespitosus (MEMC) could protect against oxidative damage caused by hydrogen peroxide (H₂O₂) in C2C12 murine myoblasts. Our results revealed that MEMC could suppress H₂O₂-induced growth inhibition and DNA damage while blocking the production of reactive oxygen species. In H₂O₂-treated cells, cell cycle progression was halted at the G2/M phase, accompanied by changes in expression of key cell cycle regulators. However, these effects were attenuated by MEMC. In addition, we found that MEMC protected cells from induction of apoptosis associated with mitochondrial impairment caused by H₂O₂ treatment. Furthermore, MEMC enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) and expression and activity of heme oxygenase-1 (HO-1) in H₂O₂-treaetd C2C12 myoblasts. However, such anti-apoptotic and cytoprotective effects of MEMC were greatly abolished by HO-1 inhibitor, suggesting that MEMC could increase Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress.

• Journal of Microbiology and Biotechnology
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• v.19 no.8
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• pp.803-809
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• 2009

Recent evidence has revealed the occurrence of an apoptotic phenotype in Candida albicans that is inducible with environmental stresses such as acetic acid, hydrogen peroxide, and amphotericin B. In the present study, we found that the Chinese herbal medicine Baicalein (BE), which was one of the skullcapflavones, can induce apoptosis in C. albicans. The apoptotic effects of BE were detected by flow cytometry using Annexin V-FITC and DAPI, and it was confirmed by transmission electron microscopy analysis. After exposure to 4 ${\mu}g$/ml BE for 12 h, about 10% of C. albicans cells were apoptotic. Both the increasing intracellular levels of reactive oxygen species (ROS) and upregulation of some redox-related genes (CAP1, SOD2, TRR1) were observed. Furthermore, we compared the survivals of CAP1 deleted, wild-type, and overexpressed strains and found that Cap1p attenuated BE-initiated cell death, which was coherent with a higher mRNA level of the CAP1 gene. In addition, the mitochondrial membrane potential of C. albicans cells changed significantly (p<0.001) upon BE treatment compared with control. Taken together, our results indicated that BE treatment induced apoptosis in C. albicans cells, and the apoptosis was associated with the breakdown of mitochondrial membrane potential.

• Journal of Korean Ophthalmic Optics Society
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• v.9 no.1
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• pp.173-180
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• 2004

This study aims to investigate the effects of hydrogen peroxide and grapefruit seed extract used as a chemical and natural disinfectants on human conjunctival cells in vitro. The main component of grapefruit seed extract is a narigin. It is one of the flavonoid types in citrus fruits and f1avonoids are widely recognized as naturally occurring(삭제) antioxidants. Cytotoxicity was determined by mitochondrial activity(MTT assay) and DNA damage was analyzed by measuring Comet assay. In LDH assay, 5% of grapefruits seed extract has been observed as a material is giving recovery effect of damaged cultured conjuctival cells by hydrogen peroxide. And also, each of concentrations has been treated simultaneously with same amounts and cytotoxicity of hydrogen peroxide and grapefruit seed extract have been estimated by LDH leakage assay after 24 hours. In conclusion, H2O2-induced cytotoxicity, apoptosis were Significantly prevented by grapefruit seed extract. It is a main component of bioflavonoids that we can simply take it as food. The present results suggest that grapefruit seed extract is a useful disinfectanct having antioxidant and antiapoptopic activity as a natural product.

• Journal of Dental Anesthesia and Pain Medicine
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• v.16 no.4
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• pp.295-302
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• 2016

Background: Reactive oxygen species play critical roles in homeostasis and cell signaling. Dexmedetomidine, a specific agonist of the ${\alpha}2$-adrenoceptor, has been commonly used for sedation, and it has been reported to have a protective effect against oxidative stress. In this study, we investigated whether dexmedetomidine has a protective effect against $H_2O_2$-induced oxidative stress and the mechanism of $H_2O_2$-induced cell death in normal human fetal osteoblast (hFOB) cells. Methods: Cells were divided into three groups: control group-cells were incubated in normoxia without dexmedetomidine, hydrogen peroxide ($H_2O_2$) group-cells were exposed to $H_2O_2$ ($200{\mu}M$) for 2 h, and Dex/$H_2O_2$ group-cells were pretreated with dexmedetomidine ($5{\mu}M$) for 2 h then exposed to $H_2O_2$ ($200{\mu}M$) for 2 h. Cell viability and apoptosis were evaluated. Osteoblast maturation was determined by assaying bone nodular mineralization. Expression levels of bone-related proteins were determined by western blot. Results: Cell viability was significantly decreased in the $H_2O_2$ group compared with the control group, and this effect was improved by dexmedetomidine. The Hoechst 33342 and Annexin-V FITC/PI staining revealed that dexmedetomidine effectively decreased $H_2O_2$-induced hFOB cell apoptosis. Dexmedetomidine enhanced the mineralization of hFOB cells when compared to the $H_2O_2$ group. In western blot analysis, bone-related protein was increased in the Dex/$H_2O_2$ group. Conclusions: We demonstrated the potential therapeutic value of dexmedetomidine in $H_2O_2$-induced oxidative stress by inhibiting apoptosis and enhancing osteoblast activity. Additionally, the current investigation could be evidence to support the antioxidant potential of dexmedetomidine in vitro.

• 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.

• Journal of Microbiology and Biotechnology
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• v.33 no.5
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• pp.591-599
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• 2023

Fisetin is a bioactive flavonol molecule and has been shown to have antioxidant potential, but its efficacy has not been fully validated. The aim of the present study was to investigate the protective efficacy of fisetin on C2C12 murine myoblastjdusts under hydrogen peroxide (H₂O₂)-induced oxidative damage. The results revealed that fisetin significantly weakened H₂O₂-induced cell viability inhibition and DNA damage while blocking reactive oxygen species (ROS) generation. Fisetin also significantly alleviated cell cycle arrest by H₂O₂ treatment through by reversing the upregulation of p21WAF1/CIP1 expression and the downregulation of cyclin A and B levels. In addition, fisetin significantly blocked apoptosis induced by H₂O₂ through increasing the Bcl-2/Bax ratio and attenuating mitochondrial damage, which was accompanied by inactivation of caspase-3 and suppression of poly(ADP-ribose) polymerase cleavage. Furthermore, fisetin-induced nuclear translocation and phosphorylation of Nrf2 were related to the increased expression and activation of heme oxygenase-1 (HO-1) in H₂O₂-stimulated C2C12 myoblasts. However, the protective efficacy of fisetin on H₂O₂-mediated cytotoxicity, including cell cycle arrest, apoptosis and mitochondrial dysfunction, were greatly offset when HO-1 activity was artificially inhibited. Therefore, our results indicate that fisetin as an Nrf2 activator effectively abrogated oxidative stress-mediated damage in C2C12 myoblasts.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.391-397
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• 2010

E2F transcription factors and their target genes have been known to play an important role in cell growth control. We found that curcumin, a polyphenolic phytochemical isolated from the plant Curcuma longa, markedly suppressed E2F4 expression in HCT116 colon cancer cells. Hydrogen peroxide was also found to decrease E2F4 protein level, indicating the involvement of reactive oxygen species (ROS) in curucmin-induced downregulation of E2F4 expression. Involvement of ROS in E2F4 downregulation in response to curcumin was confirmed by the result that pretreatment of cells with N-acetylcystein (NAC) before exposure of curcumin almost completely blocked the reduction of E2F4 expression at the protein as well as mRNA level. Anti-proliferative effect of curcumin was also suppressed by NAC which is consistent to previous reports showing curcumin-superoxide production and induction of poly (ADP-ribose) polymerase (PARP) cleavage as well as apoptosis. Expression of several genes, cyclin A, p21, and p27, which has been shown to be regulated in E2F4-dependent manner and involved in the cell cycle progression was also affected by curcumin. Moreover, decreased (cyclin A) and increased (p21 and p27) expression of these E2F4 downstream genes by curcumin was restored by pretreatment of cells with NAC and E2F4 overexpression which is induced by doxycycline. In addition, E2F4 overexpression was observed to partially ameliorate curcumin-induced growth inhibition by cell viability assay. Taken together, we found curcumin-induced ROS down-regulation of E2F4 expression and modulation of E2F4 target genes which finally lead to the apoptotic cell death in HCT116 colon cancer cells, suggesting that E2F4 appears to be a novel determinant of curcumin-induced cytotoxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.8
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• pp.1072-1078
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• 2012

The potential antioxidant and anti-inflammatory effect of water and ethanol extracts from Flammulina velutipes (Curtis) Singer (FVS) on hydrogen peroxide ($H_2O_2$) and LPS-induced oxidative damage in PC-12 and RAW264.7 cells were investigated. The DPPH radical scavenging activities of the water extract from FVS was the highest, and the 50% inhibitory concentration value was 0.388 mg/mL. Also, the antioxidant activities of water and ethanol extracts were determined by ferric reducing antioxidant power, 2,2'-azino-bis-(3-ethybenzothiazoline-6-sulphonic acid) radical scavenging activity. In addition, water extract from FVS showed a strongly inhibitory effect on lipid peroxidation by measuring ferric thiocyanate values. The water extract decreased cell apoptosis in PC-12 cells against $H_2O_2$-induced oxidative damage. In addition, FVS extracts exhibited the strongest nitric oxide (NO) inhibition activity. It was also found that FVS extract inhibited LPS-induced iNOS and COX-2 expression in RAW264.7 cells. The findings of the present study suggest that extracts of FVS exhibit anti-oxidative and anti-inflammatory activity against oxidative stress and/or stimulated cells.

• Journal of Life Science
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• v.27 no.9
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• pp.1070-1077
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• 2017

Chondrocyte apoptosis induced by reactive oxygen species (ROS) plays an important role in the pathogenesis of osteoarthritis. Schisandrin A, a bioactive compound found in fruits of the Schisandra genus, has been reported to possess multiple pharmacological and therapeutic properties. Although several studies have described the antioxidant effects of analogues of schisandrin A, the underlying molecular mechanisms of this bioactive compound remain largely unresolved. The present study investigated the cytoprotective effect of schisandrin A against oxidative stress (hydrogen peroxide [$H_2O_2$]) in SW1353 human chondrocyte cells. The results showed that schisandrin A preconditioning significantly inhibited $H_2O_2-induced$ growth inhibition and apoptotic cell death by blocking the degradation of poly (ADP-ribose) polymerase proteins and down-regulating pro-caspase-3. These antiapoptotic effects of schisandrin A were associated with attenuation of mitochondrial dysfunction and normalization of expression changes of proapoptotic Bax and antiapoptotic Bcl-2 in $H_2O_2-stimulated$ SW1353 chondrocytes. Furthermore, schisandrin A effectively abrogated $H_2O_2-induced$ intracellular ROS accumulation and phosphorylation of histone H2AX at serine 139, a widely used marker of DNA damage. Thus, the present study demonstrates that schisandrin A provides protection against $H_2O_2-induced$ apoptosis and DNA damage in SW1353 chondrocytes, possibly by prevention of ROS generation. Collectively, our data indicate that schisandrin A has therapeutic potential in the treatment of oxidative disorders caused by overproduction of ROS.