• Korean Journal of Fisheries and Aquatic Sciences
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• v.48 no.3
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• pp.354-361
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• 2015

Mitochondrial heat shock protein 75 (mtHSP75) is a member of the HSP90 family and plays essential roles in refolding proteins of the mitochondrial matrix. Mitochondria provide energy in the form of ATP and generate reactive oxygen species (ROS). Heat shock proteins (HSPs) are activated in response to stress, and protect cells. In this study, we characterized the mtHSP75 of the big-belly seahorse Hippocampus abdominalis. The protein (BsmtHSP75) is encoded by an open reading frame (ORF) of 2,157 nucleotides, has 719 amino acids (aa), and is of molecular mass 82 kDa. BsmtHSP75 has two functional domains, a histidine kinase-like ATPase (HATPase_c) domain (123-276 aa) and an HSP90 family domain (302-718 aa). BsmtHSP75 was expressed in all tested tissues of healthy seahorses. The ovary contained the highest transcription level, followed (in order) by the blood, brain, and muscle. Pouch tissue showed the lowest expression level. The expression of BsmtHSP75 was significantly (P<0.05) up-regulated on viral or bacterial challenge, suggesting that BsmtHSP75 plays a role in the immune defense against bacterial and viral pathogens.

• Journal of Radiation Protection and Research
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• v.40 no.3
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• pp.187-193
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• 2015

Deleterious effects of high dose radiation exposure with high-dose-rate are unarguable, but they are still controversial in low-dose-rate. The regulator of G-protein signaling (RGS) is a negative regulator of G protein-coupled receptor (GPCR) signaling. In addition, it is reported that irradiation stress led to GPCR-mediated mitogen-activated protein kinase (MAPK) and phosphotidylinositol 3-kinase (PI3-k) signaling. The RGS mRNA expression profiles by whole body radiation with low-dose-rate has not yet been explored. In the present study, we, therefore, examined which RGS was modulated by the whole body radiation with low-dose-rate ($3.49mGy{\cdot}h^{-1}$). Among 16 RGS expression tested, RGS6, RGS13 and RGS16 mRNA were down-regulated by low-dose-rate irradiation. This is the first report that whole body radiation with low-dose-rate can modulate the different RGS expression levels. These results are expected to reveal the potential target and/or the biomarker proteins associated with male testis toxicity induced by low-dose-rate irradiation, which might contribute to understanding the mechanism beyond the testis toxicity.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.250-257
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• 2023

Glutamate is an excitatory neurotransmitter distributed in the central nervous system of mammals. However, high concentrations of glutamate are known to cause neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and stroke by causing nerve cell death. In this study, the antioxidant activity and neuroprotective effect of subtropical natural products were analyzed. Among 11 subtropical plant extracts mainly tested, Sallacca wallichiana extract (SE) showed the greatest free radical scavenging activity. Then, we confirmed through WST-1 assay that SE protected HT22 cells against glutamate-induced cell death in a concentration-dependent manner. The protective effects of SE against glutamate-induced apoptosis in HT22 cells were also confirmed by flow cytometry analysis using Annexin V/PI double staining. We also confirmed using H₂DCF-DA single staining that SE inhibits glutamate-induced intracellular reactive oxygen species. And we were confirmed through that SE inhibited glutamate-induced phosphorylation of Mitogen-activated Protein kinases. Consequently, our results propose that SE may contribute to the development of therapeutics to prevent neurodegenerative diseases.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2003.10a
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• pp.13-13
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• 2003

When plants are infected by plant pathogens, rapid cell responses are initiated for further inhibition from fast invasion of pathogens. Hypersensitive response (HR) of plant is well known defense response stopping pathogenesis process through rapid cell death. However, informations on the signaling pathway from reception of pathogen by host plants to appropriate resistant responses are very limited to date. Efficient perception of infection by pathogens and well-programmed signalling mechanism for appropriate responses are important for survival of plants. Plant have developed a sophisticated network(s) of defense/stress responses, among which one of the earliest signalling pathways after perception (of stimuli) is the evolutionary conserved Rop GTPase and mitogen-activated protein kinase (MAPK) cascade.(중략)

• Proceedings of the Korean Environmental Sciences Society Conference
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• 2020.10a
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• pp.218-218
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• 2020

Astaxanthin, a natural antioxidant carotenoid, has been thought to provide health benefits by decreasing the risk of oxidative stress?related diseases. In the present study, we investigated the effect of an astaxanthin during the autophagic cell death induced by bisphenol A (BPA) which is known major environmental pollutants. We found that astaxanthin significantly blocked the autophagic cell death via inhibition of intracellular Reactive Oxygen Species (ROS) in normal human dermal fibroblasts. Astaxanthin significantly inhibited the phosphorylation mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) responsible for the expression of LC3-II and Beclin-1 in BPA-treated normal human dermal fibroblasts. We suggest that astaxanthin blocks autophagic cell death induced by BPA via the inhibition of ROS-mediated signaling events in human dermal fibroblasts.

• Food Science and Preservation
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• v.31 no.4
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• pp.590-600
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• 2024

Angelica keiskei, a perennial herb from Apiaceae family, has been reported to improve diabetes, inhibit thrombosis, alleviate dyslipidemia, and prevent type 2 diabetes, obesity, and atherosclerosis. In this study, the protective effects of A. keiskei extract (AKE) against tumor necrosis factor-alpha (TNF-α)-induced oxidative stress and vascular inflammation in human umbilical vein endothelial cells (HUVECs) were investigated through cell viability analysis, antioxidant enzyme analysis, western blotting, and immunofluorescence staining. The results demonstrated that pretreatment of Angelica keiskei with AKE significantly inhibited the expression of key adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 induced by TNF-α. AKE also showed a substantial reduction in intracellular reactive oxygen species levels and an increase in antioxidant enzyme activity, indicating potential antioxidant capabilities. This study further explained that AKE interfered with the nuclear factor-kappa B (NF-κB) pathway by inhibiting phosphorylation of IκBα and NF-κB, thereby preventing nuclear translocation. Additionally, AKE selectively inhibited the activation of c-Jun N-terminal kinase (JNK) within the mitogen-activated protein kinase (MAPK) pathway, revealing a specific action mechanism. These findings collectively suggest that AKE possesses multi-faceted protective properties, making it a potential therapeutic agent for inflammatory conditions and early atherosclerosis.

• Proceedings of the Microbiological Society of Korea Conference
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• 2007.05a
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• pp.120-122
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• 2007

All living organisms use numerous signal-transduction pathways to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding of these communication processes and provides a platform for therapeutic intervention when these pathways malfunction in disease states, including infection. Owing to the expanding availability of sequenced genomes, a wealth of genetic and molecular tools and the conservation of signalling networks, members of the fungal kingdom serve as excellent model systems for more complex, multicellular organisms. Here, we employed Cryptococcus neoformans as a model system to understand how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental stresses, including osmoticshock, UV, high temperature, oxidative stress and toxic drugs/metabolites. The stress-activated p38/Hog1 MAPK pathway is structurally conserved in many organisms as diverse as yeast and mammals, but its regulation is uniquely specialized in a majority of clinical Cryptococcus neoformans serotype A and D strains to control differentiation and virulence factor regulation. C. neoformans Hog1 MAPK is controlled by Pbs2 MAPK kinase (MAPKK). The Pbs2-Hog1 MAPK cascade is controlled by the fungal "two-component" system that is composed of a response regulator, Ssk1, and multiple sensor kinases, including two-component.like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. We also identified and characterized the Ssk2 MAPKKK upstream of the MAPKK Pbs2 and the MAPK Hog1 in C. neoformans. The SSK2 gene was identified as a potential component responsible for differential Hog1 regulation between the serotype D sibling f1 strains B3501 and B3502 through comparative analysis of their meiotic map with the meiotic segregation of Hog1-dependent sensitivity to the fungicide fludioxonil. Ssk2 is the only polymorphic component in the Hog1 MAPK module, including two coding sequence changes between the SSK2 alleles in B3501 and B3502 strains. To further support this finding, the SSK2 allele exchange completely swapped Hog1-related phenotypes between B3501 and B3502 strains. In the serotype A strain H99, disruption of the SSK2 gene dramatically enhanced capsule biosynthesis and mating efficiency, similar to pbs2 and hog1 mutations. Furthermore, ssk2, pbs2, and hog1 mutants are all hypersensitive to a variety of stresses and completely resistant to fludioxonil. Taken together, these findings indicate that Ssk2 is the critical interface protein connecting the two-component system and the Pbs2-Hog1 pathway in C. neoformans.

• Molecules and Cells
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• v.37 no.9
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• pp.672-684
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• 2014

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

• KSBB Journal
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• v.20 no.1 s.90
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• pp.21-25
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• 2005

Paraquat, a widely used herbicide, has been suggested as a potential risk factor for Parkinson's disease. Heme oxygenase-1(HO-1), a marker for oxidative stress and endoplasmic reticulum(ER) stress, is known to catalyze heme to biliverdin, carbon monoxide and free iron in response to various stimuli. Here we show that paraquat activates HO-1 expression in a time-and dose-dependent manner in substantia nigra(SN) dopaminergic neuronal cells. Activation of Ho-1 by paraquat was regulated primarily at the level of gene transcription. Deletion analysis of the promoter and the 5' distal enhancers, E1 and E2, of the HO-1 gene revealed that the E2 enhancer is a potent inducer of the paraquat-dependent Ho-1 gene expression in dopamninergic neuronal cells. Mutational analysis of the E2 enhacer further demonstrated that the transcription factor activator protein-1(AP-1) plays an important role in mediating paraquat-induced HO-1 gene transcription. Moreover, using specific inhibitors of the mitogen-activated protein kinases(MAPKs), we investigated the role of paraquat and MAPKs for HO-1 gene regulation in dopaminergic cells. The c-Jun N-terminal kinase(JNK) inhibitor SP600125 significantly suppressed the expression of HO-1 by paraquat. All these results demonstrate that induction of HO-1 by paraquat requies the activation of the AP-1 and JNK pathway.