• Molecules and Cells
• /
• v.41 no.12
• /
• pp.1061-1071
• /
• 2018

From Xenopus embryo studies, the BMP4/Smad1-targeted gene circuit is a key signaling pathway for specifying the cell fate between the ectoderm and neuro-ectoderm as well as the ventral and dorsal mesoderm. In this context, several BMP4/Smad1 target transcriptional factors have been identified as repressors of the neuro-ectoderm. However, none of these direct target transcription factors in this pathway, including GATA1b, Msx1 and Ventx1.1 have yet been proven as direct repressors of early neuro-ectodermal gene expression. In order to demonstrate that Ventx1.1 is a direct repressor of neuro-ectoderm genes, a genome-wide Xenopus ChIP-Seq of Ventx1.1 was performed. In this study, we demonstrated that Ventx1.1 bound to the Ventx1.1 response cis-acting element 1 and 2 (VRE1 and VRE2) on the promoter for zic3, which is a key early neuro-ectoderm gene, and this Ventx1.1 binding led to repression of zic3 transcription. Site-directed mutagenesis of VRE1 and VRE2 within zic3 promoter completely abolished the repression caused by Ventx1.1. In addition, we found both the positive and negative regulation of zic3 promoter activity by FoxD5b and Xcad2, respectively, and that these occur through the VREs and via modulation of Ventx1.1 levels. Taken together, the results demonstrate that the BMP4/Smad1 target gene, Ventx1.1, is a direct repressor of neuro-ectodermal gene zic3 during early Xenopus embryogenesis.

• Environmental Analysis Health and Toxicology
• /
• v.29
• /
• pp.10.1-10.6
• /
• 2014

Objectives Cigarette smoking had been recorded as the main cause of impaired endothelium-dependent vasodilation in smokers by reducing nitric oxide (NO), a production of endothelial nitric oxide synthase (eNOS). However, the mechanism of NO impairment via eNOS activity is unclear until now. In this study, cell passage is suggested to be a relevant factor to eNOS expression under cigarette smoking stress. Methods Bovine aortic endothelial cells (BAECs) were chosen as the research subject with passages ranking from 6 to 9 (6P to 9P). After exposure of cigarette smoking extract (CSE) solution, MTT assay and Western blot method were performed to check the cell viability as well as eNOS protein concentration. In these experiments, four concentrations of CSE at 0.5, 1, 2, and 4% were selected for treatment. Results Our results showed that cells almost died at 4% of CSE. Besides, eNOS protein mass had a linear decrease under the increase of CSE concentration. In addition, the effect of CSE on eNOS expression was dissimilar between different passages. Conclusions This study indicated that CSE had effect on both cell viability and eNOS expression. Besides, a reduction in protein mass was matched with the decrease of cell viability due to CSE tress. Last but not least, the response of eNOS protein to different concentration of CSE at different passages was disparate, making the hypothesis about cell passage related inhibition of eNOS caused by CSE solution.

• Molecular & Cellular Toxicology
• /
• v.5 no.2
• /
• pp.133-140
• /
• 2009

Caveolin may be a molecular target for modulation of aging process in cochlear hair cells and have association with oxotoxicity. First we investigated the basal expression of caveolin-1, caveolin-2, caveolin-3, nitric oxide synthase, and superoxide dismutase in UB/OC-1 cochlear hair cell line. By using a RNA interference technique, we investigated whether down-regulation of caveolin influenced telomerase activity and reactive oxygen species (ROS) production in cochlear hair cells. In addition, cisplatin and gentamycin, known ototoxic drugs, were administered to the cochlear cells to determine their impact on caveolin expression. Further attempts at elucidating cellular aging mechanism with caveolin and ototoxic drugs were carried out. The main discoveries were the presence of caveolin-1 in UB/OC-1 cells and that down-regulation of caveolin-1 reduced protein kinase A activity. Telomerase was activated by caveolin down-regulation and caveolin down-regulation inhibited oxidative stress at the mitochondrial level. When cisplatin and gentamycin were administered to the cochlear hair cells during a caveolin expression state, a decrease in telomerase activity and increase ROS activity was observed. Caveolin-1 may modulate the senescent mechanisms in cochlear cells. An increase in caveolin-1 levels can lead to ROS production in the mitochondria which may cause ototoxicity.

• Journal of Ginseng Research
• /
• v.44 no.5
• /
• pp.738-746
• /
• 2020

Background: Red ginseng contains components, including microelements, vitamins, essential oils, and fatty acids, that can be used in skincare to delay the aging process. We investigated the effects of red ginseng treatment on skin elasticity by assessing cellular stiffness and measuring collagen protein synthesis. Methods: Human dermal fibroblasts were treated with red ginseng, and the resulting changes in stiffness were investigated using atomic force microscopy. Cytoskeletal changes and mRNA expression of biomarkers of aging, including that of procollagens I and VII, elastin, and fibrillin-1, were investigated. Collagen in a human skin equivalent treated with red ginseng was visualized via hematoxylin and eosin staining, scanning electron microscopy, and atomic force microscopy. Results and conclusion: The stiffness of fibroblasts was significantly reduced by treatment with red ginseng concentrations of ≥ 0.8 mg/mL. The ratio of F-actin to G-actin decreased after treatment, which corresponded to a change in fibroblast stiffness. The storage modulus (G') and loss modulus (G'') of the skin equivalent were both lowered by red ginseng treatment. This result indicates that the viscoelasticity of the skin equivalent can be restored by red ginseng treatment.

• Korean Journal of Agricultural Science
• /
• v.46 no.3
• /
• pp.427-437
• /
• 2019

Oxidative stress and overproduction of free radicals have been reported to be a major pathological hallmark of neurodegenerative diseases. Samultang has been known as a beneficial agent to treat liver disease and cardiovascular diseases. However, the anti-oxidant activities and neuro-protective effects of Samultang against oxidative stress still have not been evaluated yet. The aim of the present study was to investigate the anti-oxidant and protective effects of Samultang and its four herbal plants, Paeonia lactiflora (PL), Ligusticum striatum (LS), Rehmannia glutinosa (RG), and Angelica gigas (AG), in vitro system and in SH-SY5Y neuronal cells. The extracts of Samultang strongly increased the radical scavenging activities of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (${\cdot}OH$), and nitric oxide (NO) in a concentration-dependent manner. Furthermore, we investigated the protective effects of Samultang on cellular damage against oxidative stress induced by hydrogen peroxide ($H_2O_2$) in SH-SY5Y cells. Treatment with Samultang alleviated the oxidative stress from $H_2O_2$ by increasing the cell viability and decreasing the intracellular reactive oxygen species levels. Based on these results, we further investigated the radical scavenging effects of PL, LS, RG, and AG. In our results, PL had the highest DPPH, ${\cdot}OH$, and NO radical scavenging activities. Thus, PL has a crucial role in Samultang, which has anti-oxidative and neuro-protective effects. The present research suggests that Samultang and PL have protective roles against oxidative stress from $H_2O_2$-induced neuronal cell death.

• IMMUNE NETWORK
• /
• v.13 no.4
• /
• pp.148-156
• /
• 2013

The $PrP^C$ is expressed in many types of immune cells including monocytes and macrophages, however, its function in immune regulation remains to be elucidated. In the present study, we examined a role for $PrP^C$ in regulation of monocyte function. Specifically, the effect of a soluble form of $PrP^C$ was studied in human monocytes. A recombinant fusion protein of soluble human $PrP^C$ fused with the Fc portion of human IgG1 (designated as soluble $PrP^C$-Fc) bound to the cell surface of monocytes, induced differentiation to macrophage-like cells, and enhanced adherence and phagocytic activity. In addition, soluble $PrP^C$-Fc stimulated monocytes to produce pro-inflammatory cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6. Both ERK and $NF-{\kappa}B$ signaling pathways were activated in soluble $PrP^C$-treated monocytes, and inhibitors of either pathway abrogated monocyte adherence and cytokine production. Taken together, we conclude that soluble $PrP^C$-Fc enhanced adherence, phagocytosis, and cytokine production of monocytes via activation of the ERK and $NF-{\kappa}B$ signaling pathways.

• Journal of the Korean Applied Science and Technology
• /
• v.33 no.1
• /
• pp.13-22
• /
• 2016

This study set its purpose on to specify whether it is possible to use wheat sprout extracts for source of cosmetics, and its biological activity. Cellular experiment was conducted to apprehend toxicity of wheat sprout extracts and through study on the whitening and aging activity of skin cell. As a result, it is appeared that wheat sprout extracts have weak toxicity for HDF, B16F10 cells. Also, it is appeared that wheat sprout extracts have weak deterrent effect on melanin biosynthesis, but since the extracts impede expression of MMP-1, which is induced UV ray, the extracts hold down the aging effect by UV rays. Hence the extracts are effective on preventing wrinkles caused by UV ray and aging. Therefore, this study is expected to be utilized usefully, if the wheat sprout extracts are used as source of functional cosmetics from the perspective of preventing skin-aging in the future.

• Journal of Ginseng Research
• /
• v.46 no.5
• /
• pp.657-665
• /
• 2022

Background: Sarcopenia is a new and emerging risk factor aggravating the quality of life of elderly population. Because Korean Red Ginseng (RG) is known to have a great effect on relieving fatigue and enhancing physical performance, it is invaluable to examine its potential as an anti-sarcopenic drug. Methods: Anti-sarcopenic effect of non-saponin fraction of Korean Red Ginseng (RGNS) was evaluated in C2C12 myoblasts treated with C2-ceramide to induce senescence phenotypes, and 22-month-old mice fed with chow diet containing 2% RGNS (w/w) for 4 further months. Results: The RGNS treatment significantly alleviated cellular senescence indicated by intracellular lipid accumulation, increased amount of lysosomal β-galactosidase, and reduced proliferative capacity in C2C12 myoblasts. This effect was not observed with saponin fraction. In an aged mouse, the 4-month-RGNS diet significantly improved aging-associated loss of muscle mass and strength, assessed by the weights of hindlimb skeletal muscles such as tibialis anterior (TA), extensor digitorum longus (EDL), gastrocnemius (GN) and soleus (SOL), and the cross-sectional area (CSA) of SOL muscle, and the behaviors in grip strength and hanging wire tests, respectively. During the same period, an aging-associated shift of fast-to slow-twitch muscle in SOL muscle was also retarded by the RGNS treatment. Conclusions: These findings suggested that the long-term diet of RGNS significantly prevented aging-associated muscle atrophy and reduced physical performance, and thus RGNS has a strong potential to be developed as a drug that prevents or improves sarcopenia.

• Journal of Animal Reproduction and Biotechnology
• /
• v.39 no.2
• /
• pp.67-80
• /
• 2024

Background: Post-ovulatory aging (POA) of oocytes is related to a decrease in the quality and quantity of oocytes caused by aging. Previous studies on the characteristics of POA have investigated injury to early embryonic developmental ability, but no information is available on its effects on mitochondrial fission and mitophagy-related responses. In this study, we aimed to elucidate the molecular mechanisms underlying mitochondrial fission and mitophagy in in vitro maturation (IVM) oocytes and a POA model based on RNA sequencing analysis. Methods: The POA model was obtained through an additional 24 h culture following the IVM of matured oocytes. NMN treatment was administered at a concentration of 25 μM during the oocyte culture process. We conducted MitoTracker staining and Western blot experiments to confirm changes in mitochondrial function between the IVM and POA groups. Additionally, comparative transcriptome analysis was performed to identify differentially expressed genes and associated changes in mitochondrial dynamics between porcine IVM and POA model oocytes. Results: In total, 32 common genes of apoptosis and 42 mitochondrial fission and function uniquely expressed genes were detected (≥ 1.5-fold change) in POA and porcine metaphase II oocytes, respectively. Functional analyses of mitochondrial fission, oxidative stress, mitophagy, autophagy, and cellular apoptosis were observed as the major changes in regulated biological processes for oocyte quality and maturation ability compared with the POA model. Additionally, we revealed that the activation of NAD⁺ by nicotinamide mononucleotide not only partly improved oocyte quality but also mitochondrial fission and mitophagy activation in the POA porcine model. Conclusions: In summary, our data indicate that mitochondrial fission and function play roles in controlling oxidative stress, mitophagy, and apoptosis during maturation in POA porcine oocytes. Additionally, we found that NAD⁺ biosynthesis is an important pathway that mediates the effects of DRP1-derived mitochondrial morphology, dynamic balance, and mitophagy in the POA model.

• BMB Reports
• /
• v.57 no.9
• /
• pp.417-423
• /
• 2024

Glucose-dependent insulinotropic polypeptide (GIP), a 42-amino-acid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging.