• Molecules and Cells
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• v.46 no.6
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• pp.329-336
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• 2023

Reactive oxygen species (ROS) serve as secondary messengers that regulate various developmental and signal transduction processes, with ROS primarily generated by NADPH OXIDASEs (referred to as RESPIRATORY BURST OXIDASE HOMOLOGs [RBOHs] in plants). However, the types and locations of ROS produced by RBOHs are different from those expected to mediate intracellular signaling. RBOHs produce O₂^•- rather than H₂O₂ which is relatively long-lived and able to diffuse through membranes, and this production occurs outside the cell instead of in the cytoplasm, where signaling cascades occur. A widely accepted model explaining this discrepancy proposes that RBOH-produced extracellular O₂^•- is converted to H₂O₂ by superoxide dismutase and then imported by aquaporins to reach its cytoplasmic targets. However, this model does not explain how the specificity of ROS targeting is ensured while minimizing unnecessary damage during the bulk translocation of extracellular ROS (eROS). An increasing number of studies have provided clues about eROS action mechanisms, revealing various mechanisms for eROS perception in the apoplast, crosstalk between eROS and reactive nitrogen species, and the contribution of intracellular organelles to cytoplasmic ROS bursts. In this review, we summarize these recent advances, highlight the mechanisms underlying eROS action, and provide an overview of the routes by which eROS-induced changes reach the intracellular space.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.165-170
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• 2012

Cell migration plays a role in many physiological and pathological processes. Reactive oxygen species (ROS) produced in mammalian cells influence intracellular signaling processes which in turn regulate various biological activities. Here, we investigated whether melanoma cell migration could be controlled by ROS production under normoxia condition. Cell migration was measured by wound healing assay after scratching confluent monolayer of B16F10 mouse melanoma cells. Cell migration was enhanced over 12 h after scratching cells. In addition, we found that ROS production was increased by scratching cells. ERK phosphorylation was also increased by scratching cells but it was decreased by the treatment with ROS scavengers, N-acetylcysteine (NAC). Tumor cell migration was inhibited by the treatment with PD98059, ERK inhibitor, NAC or DPI, well-known ROS scavengers. Tumor cell growth as judged by succinate dehydrogenase activity was inhibited by NAC treatment. When mice were intraperitoneally administered with NAC, the intracellular ROS production was reduced in peripheral blood mononuclear cells. In addition, B16F10 tumor growth was significantly inhibited by in vivo treatment with NAC. Collectively, these findings suggest that tumor cell migration and growth could be controlled by ROS production and its downstream signaling pathways, in vitro and in vivo.

• KSBB Journal
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• v.19 no.2
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• pp.110-112
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• 2004

The in vitro cell regeneration, the noni extract was mixed into the dilute noni solution and the ability of ROS to degrade noni into H$_2$O$_2$ was measured spectrophotometically. H$_2$O$_2$ was used for producing reactive oxygen species (ROS) in this measurement.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.101-107
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• 2001

Green tea catechins (GTC) and its major component, (-)-epigallocatechin gallate (EGCG) were studied for their protective effects against reactive oxygen species (ROS)-induced oxidative stress. GTC and EGCG skewed the strong antioxidative effects on the lipid peroxidation of ethyl linolate with Fenton's reagent and free radical scavenging effect to DPPH radical generation. They also protected $H_2O$$_2$- or KO$_2$-induced cytotoxicity in CHL cells or mouse splenocytes. These results indicate that GTC and EGCG are capable of protecting the lipid peroxidation, flee radical generation and cytotoxicity induced by ROS. The mechanism of inhibition in ROS-induced cytotoxicity may be due to their antiofidative and free radical scavenging properties. Therefore, GTC and EGCG may be useful chemopreventive agents by protecting the free radical generation which are involved in cancer and aging.

• Journal of Periodontal and Implant Science
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• v.39 no.3
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• pp.331-337
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• 2009

Purpose: Interleukin (IL)-8 is one of pro-inflammatory cytokines. Reactive oxygen species (ROS) are reduced metabolites of $O_2$. Aggregatibacter actinomycetemcomitans is one of representative periodontopathogens. To investigate the role of A. actinomycetemcomitans in IL-8 expression of periodontal ligament (PDL) cells, we estimated the production of IL-8 and ROS in A. actinomycetemcomitans treated PDL cells. Methods: The IL-8 production was determined by enzyme-linked immunosorbent assay. The ROS production was estimated using H2DCFDA and FACS. Results: A. actinomycetemcomitans increased the production of IL-8 and ROS at 10, 100, and 500 multiplicity of infection. N-acetylcysteine, an antioxidant of ROS, down-regulated the production of IL-8 induced by A. actinomycetemcomitans. Conclusions: These results suggest that A. actinomycetemcomitans induces IL-8 production and ROS may act as a mediator in this process.

• Genomics & Informatics
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• v.10 no.4
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• pp.244-248
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• 2012

Oxidative stress, which results in an excessive product of reactive oxygen species (ROS), is one of the fundamental mechanisms of the development of hypertension. In the vascular system, ROS have physical and pathophysiological roles in vascular remodeling and endothelial dysfunction. In this study, ROS-hypertension-related genes were collected by the biological literature-mining tools, such as SciMiner and gene2pubmed, in order to identify the genes that would cause hypertension through ROS. Further, single nucleotide polymorphisms (SNPs) located within these gene regions were examined statistically for their association with hypertension in 6,419 Korean individuals, and pathway enrichment analysis using the associated genes was performed. The 2,945 SNPs of 237 ROS-hypertension genes were analyzed, and 68 genes were significantly associated with hypertension (p < 0.05). The most significant SNP was rs2889611 within MAPK8 (p = $2.70{\times}10^{-5}$; odds ratio, 0.82; confidence interval, 0.75 to 0.90). This study demonstrates that a text mining approach combined with association analysis may be useful to identify the candidate genes that cause hypertension through ROS or oxidative stress.

• Toxicological Research
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• v.23 no.3
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• pp.215-221
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• 2007

Although sanguinarine, a benzophenanthridine alkaloid, possesses anti-cancer properties against several cancer cell lines, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood. In order to further explore the critical events leading to apoptosis in sanguinarine-treated MCF-7 human breast carcinoma cells, the following effects of sanguinarine on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 family proteins. We show that sanguinarine-induced apoptosis is accompanied by the generation of intracellular ROS and disruption of MMP as well as an increase in pro-apoptotic Bax expression and a decrease of anti-apoptotic Bcl-2 and Bcl-xL expression. The quenching of ROS generation with N-acetyl-L-cysteine, the ROS scavenger, protected the sanguinarine-elicited ROS generation, mitochondrial dysfunction, modulation of Bcl-2 family proteins, and apoptosis. Based on these results, we propose that the cellular ROS generation plays a pivotal role in the initiation of sanguinarine-triggered apoptotic death.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.485-491
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• 2011

Previously, we have reported that apigenin, a natural flavonoid found in a variety of vegetables and fruits, stimulated melanogenesis through the activation of $K^+-Cl^-$-cotransport (KCC) in B16 melanoma cells. In this study we investigated the possible involvement of reactive oxygen species (ROS) in the mechanism of apigenin-induced melanogenesis in B16 cells. Apigenin elevated intracellular ROS level in a dose-dependent manner. Treatment with various inhibitors of NADPH oxidase, diphenylene iodonium (DPI), apocynin (Apo) and neopterine (NP) significantly inhibited both the generation of ROS and melanogenesis induced by apigenin. In addition these inhibitors profoundly inhibited apigenin-induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity. However, the apigenin-induced ROS generation was not significantly affected by treatment with a specific KCC inhibitor R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA). These results indicate that the ROS production may be a upstream regulator of the apigenin-induced KCC stimulation, and in turn, melanogenesis in the B16 cells. Taken together, these results suggest that the NADPH oxidase-mediated ROS production may play an important role in the apigenin-induced melanogenesis in B16 cells. These results further suggest that NADPH oxidase may be a good target for the management of hyperpigmentation disorders.

• Journal of Korean society of Dental Hygiene
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• v.21 no.5
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• pp.545-553
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• 2021

Objectives: This study aimed to investigate the cytotoxicity of Nexus RMGIC, an indirect restorative cement, on cell survival rate and reactive oxygen species (ROS) production in periodontal stem cells (PDSCs). Methods: PDSCs were incubated with serially diluted Nexus RMGIC eluates with and without the addition of N-acetyl-cysteine (NAC). Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The ROS generation was determined by measuring the fluorescence intensity for 2',7'-dichlorofluorescin diacetate. Results: Nexus RMGIC exposure decreased cell proliferation and cell survival rate in a dose-dependent manner (1:8, 1:4, 1:2, 1:1) in PDSCs. The cytotoxicity of Nexus RMGIC was inhibited by treatment with 10-mM NAC. In addition, the production of ROS was detected by immunofluorescence after PDSCs were exposed to Nexus RMGIC. However, ROS generation was significantly suppressed in the NAC pretreatment compared with the Nexus RMGIC group. Conclusions: Nexus RMGIC increased the cytotoxicity and ROS generation. ROS was involved in Nexus RMGIC-induced cell toxicity.

• International Journal of Vascular Biomedical Engineering
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• v.2 no.2
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• pp.1-9
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• 2004

The history of studies in biology regarding reactive oxygen species (ROS) is approximately 40 years. During the initial 30 years, it appeared that these studies were mainly focused on the toxicity of ROS. However, recent studies have identified another action regarding oxidative signaling, other than toxicity of ROS. Basically, it is suggested that ROS are reactive, and degenerate to biomolecules such as DNA and proteins, leading to deterioration of cellular functions as an oxidative stress. On the other hand, recent studies have shown that ROS act as oxidative signaling in cells, resulting in various gene expressions. Recently ROS emerged as critical signaling molecules in cardiovascular research. Several studies over the past decade have shown that physiological effects of vasoactive factors are mediated by these reactive species and, conversely, that altered redox mechanisms are implicated in the occurrence of metabolic and cardiovascular diseases ROS is a collective term often used by scientist to include not only the oxygen radicals($O2^{-{\cdot}},\;{^{\cdot}}OH$), but also some non-radical derivatives of oxygen. These include hydrogen peroxide, hypochlorous acid (HOCl) and ozone (O3). The superoxide anion ($O2^{-{\cdot}}$) is formed by the univalent reduction of triplet-state molecular oxygen ($^3O_2$). Superoxide dismutase (SOD)s convert superoxide enzymically into hydrogen peroxide. In biological tissues superoxide can also be converted nonenzymically into the nonradical species hydrogen peroxide and singlet oxygen ($^1O_2$). In the presence of reduced transition metals (e.g., ferrous or cuprous ions), hydrogen peroxide can be converted into the highly reactive hydroxyl radical (${^{\cdot}}OH$). Alternatively, hydrogen peroxide may be converted into water by the enzymes catalase or glutathione peroxidase. In the glutathione peroxidase reaction glutathione is oxidized to glutathione disulfide, which can be converted back to glutathione by glutathione reductase in an NADPH-consuming process.