• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.1 s.55
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• pp.17-22
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• 2006

Phosphatidyiserine (PS) is a phospholipid which plays the structural role in membranes and serves as a cofactor of signaling enzymes for diverse cellular functions. In this study, we observed that topical treatment with PS significantly decreased trans-epidermal water loss (TEWL) induced by tape-stripping in hairless mice. Also, ceramides in epidermis were increased in PS-treated group compared to vehicle-treated one in vivo. the amounts of non-hydroxyl ceramide (NHCER) (1.4 fold) and glucosylceramide (glucosylCER) (1.6 fold), in the skin of hairless mice, were increased by topical treament with PS. Also, we demonstrated that PS stimulated keratinocyte differentiation. We observed that PS treatment morphologically altered normal human keratinocyte (NHK) from the proliferating phase to the differentiating one, suggesting that PS stimulated epidermal differentiation in NHK. We also showed that the expressions of the specific markers for epidermal differentiation, involucrin (INV) (3.5 fold up) and transglutaminase 1 (TG'ase 1) (3 fold up), were significantly increased by PS treatment, compared to untreated control in vitro. In addition, topical treatment with PS resulted in a progressive increase in INV and loricrin protein levels in vivo. In conclusion, we provide the first evidence for the physiological activities of PS in skin, and we suggest that PS strengthen the epidermal permeability harrier by stimulation of keratinocyte differentiation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5311-5316
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• 2014

Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.126-135
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• 2001

Quinacrine (QU), a phospholipase-A2 (PLA-2) inhibitor has been used clinically as a chemotherapeutic adjuvant. To understand the mechanisms leading to its chemotherapeutic effect, we have investigated QU-induced apoptotic signaling pathways in human cervical squamous carcinoma HeLa cells. In this study, we found that QU induced cytochrome c-dependent apoptotic signaling. The release of pro-apoptotic cytochrome c was QU concentration- and time-dependent, and preceded activation of caspase-9 and -3. Flow cytometric FACScan analysis using fluorescence intensities of $DiOC_6$/ demonstrated that QU-induced cytochrome c release was independent of mitochondrial permeability transition (MPT), since the concentrations of QU that induced cytochrome c release did not alter mitochondrial membrane potential (${\blacktriangle}{\Psi}_m$). Moreover, kinetic analysis of caspase activities showed that cytochrome c release led to the activation of caspase-9 and downstream death effector caspase-3, Caspase-3 inhibitor (Ac-DEVD-CHO) partially blocked QU-induced apoptosis, suggesting the importance of caspase-3 in this apoptotic signaling mechanism. Supplementation with arachidonic acid (AA) sustained caspase-3 activation induced by QU. Using inhibitors against cellular arachidonate metabolism of lipooxygenase (Nordihydroxyguaiaretic Acid, NDGA) and cyclooxygenase (5,8,11,14-Eicosatetraynoic Acid, ETYA) demonstrated that QU-induced apoptotic signaling may be dependent on its role as a PLA-2 inhibitor. Interestingly, NDCA attenuated QU-induced cytochrome c release, caspase activity as well as apoptotic cell death. The blockade of cytochrome c release by NDCA was much more effective than that attained with cyclosporin A (CsA), a MPT inhibitor. ETYA was not effective in blocking cytochrome c release, except under very high concentrations. Caspase inhibitor z-VAD blocked the release of cytochrome c suggesting that this signaling event is caspase dependent, and caspase-8 activation may be upstream of the mitochondrial events. In summary, we report that QU induced cytochrome c-dependent apoptotic signaling cascade, which may be dependent on its role as a PLA-2 inhibitor. This apoptotic mechanism induced by QU may contribute to its known chemotherapeutic effects.

• Molecules and Cells
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• v.38 no.12
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• pp.1064-1070
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• 2015

Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10-100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO ($0.1-0.5{\mu}m$), a specific mitochondrial antioxidants, and cyclosporin A ($1-5{\mu}m$), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam ($1-50{\mu}m$), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells.

• Mycobiology
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• v.45 no.4
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• pp.297-311
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• 2017

Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin $[IL]-1{\beta}$, tumor necrosis factor ${\alpha}$, IL-6, IL-8, interferon ${\gamma}$, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules ($CD8^+$ and $CD4^+$) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as $200{\mu}g/mL$ and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.

• The Journal of the Korea Contents Association
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• v.21 no.2
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• pp.85-99
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• 2021

Graphene, called the "dream material" is drawing attention as a groundbreaking new material that will lead the era of the 4th Industrial Revolution. Graphene has high strength, excellent electrical and thermal conductivity, excellent optical permeability, and excellent gas barrier properties. In this paper, as the South Korean government recently announced Green New Deal and Digital New Deal policy, we analyze graphene technology, which is also attracting attention for its application to Corona 19 biosensor, to understand its national R&D trend and knowledge structure, and to explore the possibility of its application. Firstly, 4,054 cases of national R&D project information for the last 10 years are collected from the National Science & Technology Information Service(NTIS) to analyze the trend of graphene-related R&D. Besides, projects classified as green technology are analyzed concerning the government's Green New Deal policy. Secondly, text mining analysis is conducted by collecting 500 recent graphene-related articles from e-newspapers. According to the analysis, the field with the largest number of projects was found to be high-efficiency secondary battery technology, and the proportion of total research funds was also the highest. It is expected that South Korea will lead the development of graphene technology in the future to become a world leader in diverse industries including electric vehicles, cellular phone batteries, next-generation semiconductors, 5G, and biosensors.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.

• The Korean Journal of Physiology
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• v.18 no.1
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• pp.19-35
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• 1984

Since the first report of Drury and $Szent-Gy{\ddot{o}}rgyi$ in 1929, the inhibitory influences of adenosine on the heart have repeatedly been described by many investigators. These studies have shown that adenosine and adenine nucleotides have overall depressant effects, similar to those of acetylcholine. Heart beats become slow and weak. It is also well known that adenosine is a potent endogenous coronary vasodilator. Many investigations on the working mechanisms of adenosine have been focused mainly on the effects of the coronary blood flow. However, the cellular mechanisms underlying the inhibitory action of adenosine on sinus node are not well understood yet. Thus, this study was undertaken to examine the behavior of rabbit SA node under influence of adenosine. In these series of experiments three kinds of preparations were used: whole atrial pair, left atrial strip, and isolated SA node preparations. The electrical activity of SA node was recorded with conventional glass microelectrodes 30 to 50 $M{\Omega}$. The preparations were superfused with bicarbonate-buffered Tyrode solution of pH 7.35 and aerated with a gas mixture of $3%\;CO_2-97%\;O_2$ at $35^{\circ}C$. In whole atrial pair, adenosine suppressed sinoatrial rhythm in a dose-dependent manner. Effect of adenosine on atrial rate appeared at the concentration of $10^{-5}M$ and was enhanced in parallel with the increase in adenosine concentration. Inhibitory action of adenosine on pacemaker activity was more prominent in the preparation pretreated with norepinephrine, which can steepen the slope of pacemaker potential by increasing permeability of $Ca^{+2}$. Calcium ions in perfusate slowly produced a marked change in sinoatrial rhythm. Elevation of the calcium concentration from 0.3 to 8 mM increased the atrial rate from 132 to 174 beats/min, but over 10 mM $Ca^{+2}$ decreased. The inhibitory effect of adenosine on sinoatrial rhythm developed very rapidly. Atrial rate was recovered promptly from the adenosine-induced suppression by the addition of norepinephrine, but extra $Ca^{+2}$ was less suitable to restore the suppression of atrial rate. Adenosine suppressed also atrial contractility in the same dosage range that restricted pacemaker activity, even in the reserpinized preparation. In isolated SA node preparation, spontaneous firing rate of SA node at $35^{\circ}C$(mean{\pm}SEM, n=16) was $154{\pm}3.3\;beats/min. The parameters of action potentials were: maximum diastolic potential(MDP), $-73{\pm}1.7\;mV: overshoot(OS), $9{\pm}1.4\;mV: slope of pacemaker potential(SPP), $94{\pm}3.0\;mV/sec. Adenosine suppressed the firing rate of SA node in a dose-dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}M$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine and propranolol. Lowering extra $Ca^{2+}$ irom 2 mM to 0.3 mM resulted in a marked decrease of OS and SPP, but almost no change of MDP. However, increase of perfusate $Ca^{2+}$ from 2 mM to 6 or 8 mM produced a prominent decrease of MDP and a slight increase of OS and SPP. Dipyridamole(DPM), which is known to block the adenosine transport across the cell membrane, definately potentiated the action of adenosine. The results of this experiment suggest that adenosine suppressed pacemaker activity and atrial contractility simultaneously and directly, by decreasing $Ca^{2+}-permeability$ of nodal and atrial cell membranes.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.540-548
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• 2001

Backgrounds : Because ventilator-induced lung injury is partly dependent on the intensity of vascular flow, we hypothesized that hypothermia may attenuate the degree of such an injury through a reduced cardiac output. Methods : Twenty-seven male Sprague-Dawley rats were randomly assigned to normothermia ($37{\pm}1^{\circ}C$)-injurious ventilation (NT-V) group (n=10), hypothermia ($27{\pm}1^{\circ}C$)-injurious ventilation (HT-V) group (n=10), or nonventilated control group (n=7). The two thermal groups were subjected to injurious mechanical ventilation for 20 min with peak airway pressure 30 cm $H_2O$ at zero positive end-expiratory pressure, which was translated to tidal volume $54{\pm}6\;ml$ in the NT-V group and $53{\pm}4\;ml$ in the HT-V group (p>0.05). Results : Pressure-volume (P-V) curve after the injurious ventilation was almost identical to the baseline P-V curve in the HT-V group, whereas it was shifted rightward in the NT-V group. On gross inspection, the lungs of the HT-V group appeared smaller in size, and showed less hemorrhage especially at the dependent regions, than the lungs of the NT-V group. [Wet lung weight (g)/body weight (kg)] ($1.6{\pm}0.1$ vs $2.4{\pm}1.2$ ; p=0.014) and [wet lung weight/dry lung weight] ($5.0{\pm}0.1$ vs $6.1{\pm}0.8$ ; p=0.046) of the HT-V group were both lower than those of the NT-V group, while not different from those of the control group($1.4{\pm}0.4$, $4.8{\pm}0.4$, respectively). Protein concentration of the BAL fluid of the HT-V group was lower than that of the NT-V group($1,374{\pm}726\;ug/ml$ vs $3,471{\pm}1,985\;ug/ml$;p=0.003). Lactic dehydrogenase level of the BAL fluid of the HT-V group was lower than that of the NT-V group ($0.18{\pm}0.10\;unit/ml$ vs $0.43{\pm}0.22\;unit/ml$;p=0.046). Conclusions : Hypothermia attenuated pulmonary hemorrhage, permeability pulmonary edema, and alveolar cellular injuries associated with injurious mechanical ventilation, and preserved normal P-V characteristics of the lung in rats.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.236-249
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• 1993

Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.