• Preventive Nutrition and Food Science
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• v.17 no.2
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• pp.129-135
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• 2012

GPAR{elidium (G.) amansii is a red alga widely distributed in the shallow waters around East Asian countries. We investigated the effect of G. amansii on lipid accumulation and ROS (Reactive Oxygen Species) production in 3T3-L1 cells. G. amansii extracts dose-dependently inhibited lipid formation and ROS generation in cultured cells. Our results showed that anti-adipogenic effect of G. amansii was due to the reduction in mRNA expressions of PPAR${\gamma}$(peroxisome proliferator-activated receptor-${\gamma}$) and aP2 (adipocyte protein 2). G. amansii extracts significantly decreased mRNA levels of a ROS-generator, NOX4 (nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4), and increased the protein levels of antioxidant enzymes including SOD1/2 (superoxide dismutases), Gpx (glutathione peroxidase), and GR (glutathione reductase), which can lead to the reduction of ROS in the cell. In addition, the G. amansii extract enhanced mRNA levels of adiponectin, one of the adipokines secreted from adipocytes, and GLUT4, glucose uptake protein. Taken together, our study shows that G. amansii extract inhibited lipid accumulation and ROS production by controlling adipogenic signals and ROS regulating genes.

• Journal of Plant Biotechnology
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• v.43 no.2
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• pp.231-239
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• 2016

To study the transcript levels of epigenetically regulated genes in tobacco, we have developed a transgenic line OX1 overexpressing NtROS2a gene encoding cytosine DNA demethylation and a RNAi plant line RNAi13. It has been reported that salt- and $H_2O_2$-stress tolerance of these transgenic lines are enhanced with various phenotypic characters (Lee et al. 2015). In this paper, we conducted microarray analysis with Agilent Tobacco 4 x 44K oligo chip by using overexpression line OX1, RNAi plant line RNAi 13, and wild type plant WT. Differentially expressed genes (DEGs) related to metabolism, nutrient supply, and various stressed were up-regulated by approximately 1.5- to 80- fold. DEGs related to co-enzymes, metabolism, and methylation functional genes were down-regulated by approximately 0.03- to 0.7- fold. qRT-PCR analysis showed that the transcript levels of several candidate genes in OX1 and RNAi lines were significantly (p < 0.05) higher than those in WT, such as genes encoding KH domain-containing protein, MADS-box protein, and Zinc phosphodiesterase ELAC protein. On the other hand, several genes such as those encoding pentatricopeptide (PPR) repeat-containing protein, histone deacetylase HDAC3 protein, and protein kinase were decreased by approximately 0.4- to 1.0- fold. This study showed that NtROS2a gene encoding DNA glycosylase related to demethylation could regulate adaptive response of tobacco at transcriptional level.

• Biomedical Science Letters
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• v.25 no.1
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• pp.23-31
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• 2019

The protein kinase $CK2{\alpha}$ (formerly Casein Kinase II) is implicated in tumorigenesis and transformation. However, the mechanisms of $CK2{\alpha}$ activation in breast cancer have yet to be elucidated. This study investigated the mechanisms of $CK2{\alpha}$ activation in estrogen signaling. Estrogen increased reactive oxygen species (ROS) production, $CK2{\alpha}$ activity, and protein expression in estrogen receptor positive ($ER^+$) MCF-7 human breast cancer cells, which were inhibited by the antioxidant N-acetyl-L-cysteine. $H_2O_2$ enhanced $CK2{\alpha}$ activity and protein expression. Human epidermal growth factor (EGF) increased ROS production, $CK2{\alpha}$ activity and protein expression in EGF receptor 2 (HER2)-overexpressing MCF-7 (MCF-7 HER2) cells, but not in MCF-7 cells. Estrogen induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The p38 inhibitor, SB202190, blocked estrogen-induced increases in ROS production, $CK2{\alpha}$ activity and $CK2{\alpha}$ protein expression. The data suggest that ROS/p38 MAPK is the key inducer of $CK2{\alpha}$ activation in response to estrogen or EGF.

• BMB Reports
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• v.52 no.4
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• pp.265-270
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• 2019

We investigated whether SIRT1 is associated with reactive oxygen species (ROS) accumulation during CK2 downregulation-mediated senescence. SIRT1 overexpression suppressed ROS accumulation, reduced transcription of FoxO3a target genes, and nuclear export and acetylation of FoxO3a, which were induced by CK2 downregulation in HCT116 and MCF-7 cells. Conversely, overexpression of a dominant-negative mutant SIRT1 (H363Y) counteracted decreased ROS levels, increased transcriptional activity of FoxO3a, and increased nuclear import and decreased acetylation of FoxO3a, which were induced by CK2 upregulation. CK2 downregulation destabilized SIRT1 protein via an ubiquitin-proteasome pathway in human cells, whereas CK2 overexpression reduced ubiquitination of SIRT1. Finally, the SIRT1 activator resveratrol attenuated the accumulation of ROS and lipofuscin as well as lifespan shortening, and reduced expression of the DAF-16 target gene sod-3, which were induced by CK2 downregulation in nematodes. Altogether, this study demonstrates that inactivation of the SIRT1-FoxO3a axis, at least in part, is involved in ROS generation during CK2 downregulation-mediated cellular senescence and nematode aging.

• IMMUNE NETWORK
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• v.14 no.5
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• pp.241-248
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• 2014

It is debatable whether AMP-activated protein kinase (AMPK) activation is involved in anti-apoptotic or pro-apoptotic signaling. AICAR treatment increases AMPK-${\alpha}1$ phosphorylation, decreases intracellular reactive oxygen species (ROS) levels, and significantly increases Annexin V-positive cells, DNA laddering, and caspase activity in human myeloid cell. AMPK activation is therefore implicated in apoptosis. However, AMPK-${\alpha}1$-knockdown THP-1 cells are more sensitive to apoptosis than control THP-1 cells are, suggesting that the apoptosis is AMPK-independent. Low doses of AICAR induce cell proliferation, whereas high doses of AICAR suppress cell proliferation. Moreover, these effects are significantly correlated with the downregulation of intracellular ROS, strongly suggesting that AICAR-induced apoptosis is critically associated with the inhibition of NADPH oxidase by AICAR. Collectively, our results demonstrate that in AICAR-induced apoptosis, intracellular ROS levels are far more relevant than AMPK activation.

• Nutrition Research and Practice
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• v.13 no.4
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• pp.279-285
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• 2019

BACKGROUND/OBJECTIVES: Excessive production of reactive oxygen species (ROS) such as hydroxyl (${\cdot}OH$), nitric oxide (NO), and hydrogen peroxide ($H_2O_2$) is reported to induce oxidative stress. ROS generated by oxidative stress can potentially damage glial cells in the nervous system. Cordyceps militaris (CM), a kind of natural herb widely found in East Asia. In this study, we investigated the free radical scavenging activity of the CM extract and its neuroprotective effects in $H_2O_2$-induced C6 glial cells. MATERIALS/METHODS: The ethanol extract of CM ($100-1,000{\mu}g/mL$) was used to measure DPPH, ${\cdot}OH$, and NO radical scavenging activities. In addition, hydrogen peroxide ($H_2O_2$)-induced C6 glial cells were treated with CM at $0.5-2.5{\mu}g/mL$ for measurement of cell viability, ROS production, and protein expression resulting from oxidative stress. RESULTS: The CM extract showed high scavenging activities against DPPH, ${\cdot}OH$, and NO radicals at concentration of $1,000{\mu}g/mL$. Treatment of CM with $H_2O_2$-induced oxidative stress in C6 glial cells significantly increased cell viability, and decreased ROS production. Cyclooxygenase-2 and inducible nitric oxide synthase protein expression was down-regulated in CM-treated groups. In addition, the protein expression level of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular regulated protein kinases (p-ERK) in $H_2O_2$-induced C6 glial cells was down-regulated upon CM administration. CONCLUSION: CM exhibited radical scavenging activity and protective effect against $H_2O_2$ as indicated by the increased cell viability, decreased ROS production, down-regulation of inflammation-related proteins as well as p-p38, p-JNK, and p-ERK protein levels. Therefore, we suggest that CM could play the protective role from oxidative stress in glial cells.

• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.321-325
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• 2018

In this study, we evaluated the possibility of wrinkle-reducing functional cosmetic material of isoquercitrin (IQC) isolated from Nymphoides indica (NP) by measuring the efficacy of ROS inhibition, procollagen synthesis induction, and matrix metalloproteinase (MMP)-1 inhibition. As a result, ROS tended to be inhibited in a concentration dependent manner, and the procollagen protein synthesis rate was increased by 70% ($5{\mu}g/mL$) and the MMP-1 protein was decreased by 41% ($5{\mu}g/mL$) compared with the control. This was suggested the ability of IQC to induce the procollagen synthesis and to reduce the ROS and MMP-1 production. Therefore, it is considered that IQC isolated from NP has enough value to be a functional cosmetic material.

• The Journal of Korean Obstetrics and Gynecology
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• v.35 no.3
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• pp.1-23
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• 2022

Objectives: The purpose of this study is to evaluate anti-breast cancer and anti-inflammatory effects of Chungganhaewool-tang and Shipyeukmiyeugi-eum. Methods: MDA-MB-231 cells were used to measure cytotoxicity, Reactive oxygen species (ROS) production, protein expression amounts of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Cytochrome C Caspase-3, Caspase-7, Caspase-9, Poly ADP-ribose polymerase (PARP), Nuclear factor erythroid-2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD (P) H Quinone Oxidoreductase 1 (NQO1) to evaluate the anti-breast cancer effects of Chungganhaewool-tang (CHT) and Shipyeukmiyeugi-eum (SYE), and THP-1 cells, differentiated into macrophage and induced inflammation with Lipopolysaccharide (LPS), were used to measure production amounts of ROS, Nitric oxide (NO), and protein expression amounts of Inducible nitric oxide synthase (iNOS), Cyclooxygenase (COX-2), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) to evaluate the anti-inflammatory effects of CHT and SYE. Results: CHT and SYE reduced MDA-MB-231 cell counts, increased protein expression of Bax and Cytochrome C, and decreased protein expression of Bcl-2, Bcl-xl. The protein expression amounts of Caspase-3, 7, and 9 decreased, but amounts of the active form, cleaved Caspase-3, 7, and 9, increased. In addition, PARP protein expression decreased, the amount of PARP protein in the cleaved form increased, and the amount of protein expressions of Nrf2 and HO-1 decreased, but NQO1 showed no significant difference. In THP-1 cells CHT and SYE reduced ROS and NO, and reduced protein expressions of iNOS, COX-2, IL-1, and TNF-α, but only SYE groups reduced IL-6. Conclusions: This study suggests that CHT and SYE have potential to be used as treatments for breast cancer.

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.171-177
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• 2022

ROS1 (c-ros oncogene) is one of the gene with mutation in NSCLC (non-small cell lung cancer). The increased expression of ROS1 is leading to the increase proliferation of cell, cell migration and survival. Crizotinib and Entrectinib are the drugs that have been approved by FDA against ROS1 protein, but recently patients started to develop resistance against Crizotinib and there is a need of new drug that could act as an effective drug against ROS1 for NSCLC. In this study, we have performed virtual screening, where compounds are taken from Zinc 15 dataset and molecular docking was performed. The top compounds were taken based upon their binding affinity and their interactions with the residues. The compounds stability and chemical reactivity was also studied through Density Functional theory and their properties. Further study of these compounds could reveal the required information of ROS1-inhibitor complex and in the discovery of potent inhibitors.

• Journal of Life Science
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• v.33 no.11
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• pp.851-858
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• 2023

Unique cartilage matrix-associated protein (UCMA) is an extrahepatic vitamin K-dependent protein rich in γ-carboxylated (Gla) residues. UCMA has been recognized for its ability to promote osteoblast differentiation and enhance bone formation; however, its impact on osteoblasts under hyperglycemic stress remains unknown. In this paper, we investigated the effect of UCMA on MC3T3-E1 osteoblastic cells under hyperglycemic conditions. After exposure to high glucose, the MC3T3-E1 cells were treated with recombinant UCMA proteins. CellROX and MitoSOX staining showed that the production of reactive oxygen species (ROS), which initially increased under high-glucose conditions in MC3T3-E1 cells, decreased after UCMA treatment. Additionally, quantitative polymerase chain reaction revealed increased expression of antioxidant genes, nuclear factor erythroid 2-related factor 2 and superoxide dismutase 1, in the MC3T3-E1 cells exposed to both high glucose and UCMA. UCMA treatment downregulated the expression of heme oxygenase-1, which reduced its translocation from the cytosol to the nucleus. Moreover, the expression of dynamin-related protein 1, a mitochondrial fission marker, was upregulated, and AKT signaling was inhibited after UCMA treatment. Overall, UCMA appears to mitigate ROS production, increase antioxidant gene expression, impact mitochondrial dynamics, and modulate AKT signaling in osteoblasts exposed to high-glucose conditions. This study advances our understanding of the cellular mechanism of UCMA and suggests its potential use as a novel therapeutic agent for bone complications related to metabolic disorders.