• Anatomy and Cell Biology
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• v.56 no.2
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• pp.166-178
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• 2023

Undeniably, endothelial cells (EC) contribute to the maintenance of the homeostasis of the organism through modulating cellular physiology, including signaling pathways, through the release of highly active molecules as well as the response to a myriad of extrinsic and intrinsic signaling factors. Review the data from the current literature on the EC role in norm and disease. Endothelium maintains a precise balance between the released molecules, where EC dysfunction arises when the endothelium actions shift toward vasoconstriction, the proinflammatory, prothrombic properties after the alteration of nitric oxide (NO) production and oxidative stress. The functions of the EC are regulated by the negative/positive feedback from the organism, through EC surface receptors, and the crosstalk between NO, adrenergic receptors, and oxidative stress. More than a hundred substances can interact with EC. The EC dysfunction is a hallmark in the emergence and progression of vascular-related pathologies. The paper concisely reviews recent advances in EC (patho) physiology. Grasping EC physiology is crucial to gauge their potential clinical utility and optimize the current therapies as well as to establish novel nanotherapeutic molecular targets include; endothelial receptors, cell adhesion molecules, integrins, signaling pathways, enzymes; peptidases.

• Molecules and Cells
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• v.43 no.9
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• pp.784-792
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• 2020

Arginine kinase (AK), a bioenergy-related enzyme, is distributed widely in invertebrates. The role of highly conserved histidines in AKs is still unascertained. In this study, the highly conserved histidine 284 (H284) in AK of Daphnia magna (DmAK) was replaced with alanine to elucidate the role of H284. We examined the alteration of catalytic activity and structural changes of H284A in DmAK. The catalytic activity of H284A was reduced dramatically compared to that in wild type (WT). Thus the crystal structure of H284A displayed several structural changes, including the alteration of D324, a hydrogen-bonding network around H284, and the disruption of π-stacking between the imidazole group of the H284 residue and the adenine ring of ATP. These findings suggest that such alterations might affect a conformational change of the specific loop consisting of G310-V322 at the antiparallel β-sheet region. Thus, we speculated that the H284 residue might play an important role in the conformational change of the specific loop when ATP binds to the substrate-binding site of DmAK.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.13-34
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• 2003

Fructose-1, 6-diphosphate (FOP), a glycolytic metabolite is reported to ameliorate inflammation and inhibit the nitric oxide production in murine macrophages stimulated with endotoxin. It is also reported that FOP has cytoprotective effects against hypoxia or ischemia/reperfusion injury in brain and heart. In this study, we examined whether FDP has protective effects on UV-induced oxidative damage in skin cell culture system and human skin in vivo. FDP had a protective role in UVB-induced LDH release and ROS accumulation in HaCaT although it did not show direct radical scavenging effect in the experiment using 1, 1-diphenyl-2-picrylhydrazyl (DPPH). FDP also preserved cellular GSH content after UV irradiation in HaCaT and normal human fibroblast culture system. Cellular oxidative stress induces multiple downstream signaling pathways that regulate expression of multiple gene including MMP-1 and collagen, we examined the effects of FDP on UV-induced alteration of these protein expression in fibroblast culture and human skin in vivo. The increased MMP-1 expression in fibroblast and human skin by UV irradiation was significantly decreased by FDP. FDP also prevented the UV-induced decrease of collagen expression in fibroblast and human skin. Moreover, the decreasing the intracellular levels of reducing equivalents in human fibroblast by glutathione (GSH) depletion lowered the UVA dose threshold for reduction of procollagen expression, indicating that the differences of glutathione contents define the susceptibility of fibroblasts towards UV-induced reduction of procollagen expression. FDP also preserved cellular GSH content after UV irradiation, indicating that FDP has protective effects on UV-induced reduction of procollagen expression, which are possibly through maintaining intracellular reducing equivalent. Based on these premises, we examined the effect of daily use of a moisturizer containing FDP on facial wrinkle in comparison with vehicle moisturizer lacking FDP. In the clinical study, FDP significantly decreased facial wrinkle compared with vehicle alone after 6 months of use. Our results suggest that FDP has anti-aging effects in skin by increasing cellular antioxidant system and preventing oxidative signal and inflammatory reaction. Therefore FDP may be useful anti-aging agent for cosmetic purpose.

• Molecules and Cells
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• v.40 no.4
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• pp.271-279
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• 2017

Ran-binding protein family member, RanBP9 has been reported in various basic cellular mechanisms and neuropathological conditions including schizophrenia. Previous studies have reported that RanBP9 is highly expressed in the mammalian brain and retina; however, the role of RanBP9 in retinal development is largely unknown. Here, we present the novel and regulatory roles of RanBP9 in retinal development of a vertebrate animal model, zebrafish. Zebrafish embryos exhibited abundant expression of ranbp9 in developing brain tissues as well as in the developing retina. Yeast two-hybrid screening demonstrated the interaction of RanBP9 with Mind bomb, a component of Notch signaling involved in both neurogenesis and neural disease autism. The interaction is further substantiated by co-localization studies in cultured cells. Knockdown of ranbp9 resulted in retinal dysplasia with defective proliferation of retinal cells, downregulation of neuronal differentiation marker huC, elevation of neural proliferation marker her4, and alteration of cell cycle marker p57kip2. Expression of the $M{\ddot{u}}ller$ glial cell marker glutamine synthase was also affected in knockdown morphants. Our results suggest that Mind bomb-binding partner RanBP9 plays a role during retinal cell development of zebrafish embryogenesis.

• Applied Biological Chemistry
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• v.41 no.4
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• pp.228-234
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• 1998

An adaptive measure of photosynthetic cells to a condition identified with a reduction of cellular energy charge, caused by water deficit-induced impairment of photosynthetic ATP production, was investigated using hydroponically cultured rice seedlings. Water stress treatment of the seedlings resulted in a marked decrease in cellular ATP level, a significant increase in the content of NAD(H) and concurrent decrease in that of NADP(H) in shoots, which accompanied a decrease in the activity of NAD kinase (EC 2.7.1.23) that specifically converts NAD(H) to NADP(H). The decline in the enzyme activity was particularly evident in the $Ca^{2+}/calmodulin-dependent$ kinase, the major form of NAD kinase in plants, whereas the level of active calmodulin remained unchanged during water deficit. The ratio of $NADP^+$ to NADPH was maintained nearly constant and no increases were seen in the level of $H_2O_2$ and the activities of $superoxide/H_2O_2-detoxifying$ enzymes in shoots stress-treated for two days. Based on these results, it may be suggested that rice plants take a strategy to cope with an adverse situation of limited photophosphorylation created by water deficit in that cells facilitate ATP production through glycolysis and oxidative phosphorylation; in doing so, rice cells suppress NAD kinase activity, consequently up-sizing the NAD(H) pool at the expense of the NADP(H) pool. Several parameters associated with the stress symptoms are also of implicative that there is no overproduction of superoxide radical or the related active oxygen at least in rice seedlings.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.111-115
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• 2005

Ultraviolet (UV) radiation to mammalian skin is known to alter cellular function via generation of Reactive Oxygen Species (ROS), DNA damage and DNA lesions, such as pyrimidine dimmers and photoproducts, which could lead to DNA mutation if they are not repaired. In this study, we have investigated the reduction of DNA damage and of apoptosis with a particular attention to genetic effect of paeoniflorin in Normal Human Epidermal Keratinocytes (NHEK). After UVB irradiation from $10\;to\;500mJ/cm^{2}$ to NHEK, Mean Tail Moments (MTM) were increased with UVB dose increase. The greatest amount of strand breaks was induced at $500mJ/cm^{2}$ of UVB. Even at the lowest dose of UVB ($10mJ/cm^{2}$), change in MTM was detected (P<0.0001). Pretreated cell with 0.1% paeoniflorin maximally reduced the level of DNA damage to about 21.3%, compared to untreated cell. In the lower concentrations less than 0.01% of paeoniflorin, MTM had a small increase but paeoniflorin still had reductive effects of DNA damage. We measured the apoptosis suppression of paeoniflorin with annexin V flous staining kit. As we observed under the fluorescence microscopy to detect apoptosis in the irradiated cell, the fluorescence intensity was clearly increased in the untreated cell, but decreased in treated cells with paeoniflorin. These results suggest that paeoniflorin reduces the alteration of cell membranes and prevents DNA damage. Therefore, the use of paeoniflorin as a free radical scavenger to reduce the harmful effects of UV lights such as chronic skin damage, wrinkling and skin cancer can be useful to prevent the formation of photooxidants that result in radical damage.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Molecules and Cells
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• v.28 no.6
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• pp.565-573
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• 2009

The pig could be a useful model to characterize molecular aspects determining several delicate phenotypes because they have been bred for those characteristics. The Korean native pig (KNP) is a regional breed in Korea that was characterized by relatively high intramuscular fat content and reddish meat color compared to other western breeds such as Yorkshire (YS). YS grew faster and contained more lean muscle than KNP. We compared the KNP to Yorksire to find molecular clues determining muscle characteristics. The comparison of skeletal gene expression profiles between these two breeds showed molecular differences in muscle. We found 82 differentially expressed genes (DEGs) defined by fold change (more than 1.5 fold difference) and statistical significance (within 5% of false discovery rate). Functional analyses of these DEGs indicated up-regulation of most genes involved in cell cycle arrest, down-regulation of most genes involved in cellular differentiation and its inhibition, down-regulation of most genes encoding component of muscular-structural system, and up-regulation of most genes involved in diverse metabolism in KNP. Especially, DEGs in above-mentioned categories included a large number of genes encoding proteins directly or indirectly involved in p53 pathway. Our results indicated a possible role of p53 to determine muscle characteristics between these two breeds.

• Journal of Embryo Transfer
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• v.25 no.4
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• pp.259-262
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• 2010

Optimization of the preimplantation mammalian embryo culture condition was widely focused on refining medium composition under the name of chemically defined media. However, recent research revealed that the alteration of physical environment can be a crucial factor to a successful embryo development. In this study, under the same embryo density, a novel culture device named oil-free micro tube culture (MTC) system was evaluated using porcine parthenogenetic embryos. The activated oocytes were placed into the 0.2 ml thin-wall flat cap PCR tube and cultured to the blastocyst stage. As a preliminary step, embryo density and culture medium volume were optimized under a standard drop culture system. The optimal embryo density range for in vitro culture was 0.5 embryos per ${\mu}l$ in $20\;{\mu}l$ drop (20.5%) and 1.0 embryos per ${\mu}l$ in $10\;{\mu}l$ drop (20.6%). Based on these results, we compared drop culture system and 'MTC' system in terms of the developmental rate to the blastocyst stage. In $20\;{\mu}l$ medium volume, the 'MTC' system showed similar blastocyst formation rate when compared with drop culture system (20.2% versus 20.5%, respectively) while the 'MTC' system showed lower blastocyst formation rate than drop culture system in $10\;{\mu}l$ one (12.7% versus 20.0%, respectively). Therefore the $20\;{\mu}l$ MTC system may be an alternative incubation system for short-distance embryo transport without carrying the $CO_2$ incubator and this provides novel embryo culture device to clinical veterinary embryologists.

• KSBB Journal
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• v.29 no.1
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• pp.50-57
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• 2014

NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.