• The Journal of Korean Medicine
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• v.23 no.1
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• pp.120-132
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• 2002

Objectives : The purpose of this investigation was to evaluate the effect of Goomicheongsim-won Extracts on E20 corticells and P7 cerebellar cells exposed to hypoxia, and the effect on neuronal protection by elimination of Rhinoceros unicornis L. and/or Orpiment $As_2S_3$. Methods : P7 cerebellar cells were grown in various concentrations of KM-A, KM-B, KM- C and KM-D. On 7 DIV (day in vitro), cells were exposed to hypoxia (98% $N_2/5%{;}CO_2,{\;}3{\;}hr,{\;}37^{\circ}C$) and normoxia, and then further incubated for 3 days. Neuronal viabilities were expressed as percentages of control. E20 cortical cells were grown in various concentrations of KM-A, KM-B, KM-C, and KM-D. On 7 DIV, cells were exposed to hypoxia and normoxia, and then further incubated for 3 and 7 days. Results : I. The effect of KM-A on neuronal protection was significantly increased P7 cerebellar granule cells and E20 cortical cells on normoxia and hypoxia. 2. The effect of KM-B on neuronal protection was increased P7 cerebellar granule cells on normoxia, but was significantly decreased P7 cerebellar granule cells on hypoxia. The effect of KM-B on neuronal protection was non-significantly increased E20 cortical cells on normoxia and hypoxia. 3. The effect of KM-C on neuronal protection was non-significantly increased P7 cerebellar granule cells on normoxia and hypoxia and was decreased (p=0.058) on hyperconcentration of the extracts in normoxia. The effect of KM-C on neuronal protection was significantly increased P7 cerebellar granule cells and E20 cortical cells on normoxia and hypoxia (10 DIV), and the effect was E20 cortical cells on normoxia (14 DIV), non-significantly increased E20 cortical cells on hypoxia (14DIV). 4. The effect of KM-D on neuronal protection was increased P7 cerebellar granule cells on normoxia but was not on hyperconcentration of the extracts, was significantly decreased on hyperconcentration of the extracts in hypoxia. The effect of KM-D on neuronal protection was significantly increased E20 cortical cells on normoxia and was significantly increased E20 cortical cells increased on hypoxia (10 DIV). Conclusions : Goomicheongsim-won extracts had applicable effect on E20 corticells and P7 cerebellar cells exposed to hypoxia. The effect on neuronal protection by elimination of Rhinoceros unicornis L. and/or Orpiment $As_2S_3$ was changed.

• Journal of Oriental Neuropsychiatry
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• v.22 no.2
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• pp.163-176
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• 2011

Objectives : BCS(Bambusae concretio silicae) is used as a traditional medicine in Korea for the incipient stroke. Recent reports indicated that BCS has a neuroprotective effect by anti-convulsion effect. However, it's mechanism is not well studied. The purpose of this study was to investigate into the molecular mechanism of BCS for neuroprotection in normoxia of cultured rat hippocampal neurons. Methods : BCS (1.0, 2.5, 5.0, and $10.0\;{\mu}g/m{\ell}$) was added to culture media (Neurobasal supplemented with B27) on DIV 0, given a normoxia, and the cell viability was measured by typical phase-contrast images of the cultures with 1.0, 2.5, 5.0, and $10.0\;{\mu}g/m{\ell}$ on DIV 21. Effects of BCS on the expression of various synaptic proteins ($GABA_B$ R1, $GABA_B$ R2, GlyR, PSD95) were observed by immunocytochemistry showing on DIV 3, 7 and 21. Results : Typical phase-contrast images of the cultures indicated that BCS has a protective effect of rat hippocampal cells in normoxia. The BCS upregulated $GABA_B$ R1 after normoxia on DIV 7, $GABA_A$ ${\beta}2/3$ on DIV 21 and $GABA_B$ R2 on DIV 21. And the BCS downregulated PSD95 after normoxia on DIV 7. Conclusions : The present study showed evidence for the efficacy of BCS in Typical phase-contrast images, upregulation of inhibitory neurotransmitter receptors($GABA_B$ R1) and downregulation of PSD95 which eventually protected neuronal cell death in normoxia.

• Journal of Life Science
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• v.17 no.1 s.81
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• pp.143-149
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• 2007

Scutellaria baicalensis GEORGI(SB) is used in oriental medicine for the treatment of incipient strokes. Although it has been reported that SB is neuroprotective in a hypoxia model, its mechanism is poorly understood. Here, we investigated the effect of SB on the modulation of retinoic acid receptor a (RARa). Rat cerebrocortical cells were grown in neurobasal medium. On DIV12 cells were treated with SB $(20{\mu}g/ml)$ and given a hypoxic shock $(2%\;O_2/5%\;CO_2,\;3hr)$ on DIV14. In situ hybridization using cRNA probe revealed that RARa mRNA punctae are distributed, in addition to nucleus, throughout neuronal dendrites, where SB upregulated its density by 69.8% (p=0.001) and 129.8% (p=0.001) in both normoxia and hypoxia, respectively. At the protein level, SB upregulated RARa in the neuronal soma by 78.8% (p=0.004) and 23.6% (p=0.001) in both normoxia and hypoxia, respectively. These results indicate that SB upregulates RARa in both normoxia and hypoxia, which might contribute to the neuroprotection.

• Biomaterials Research
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• v.22 no.4
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• pp.271-278
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• 2018

Background: The chondrogenic differentiation of mesenchymal stem cells (MSCs) is regulated by many factors, including oxygen tensions, growth factors, and cytokines. Evidences have suggested that low oxygen tension seems to be an important regulatory factor in the proliferation and chondrogenic differentiation in various MSCs. Recent studies report that synovium-derived mesenchymal stem cells (SDSCs) are a potential source of stem cells for the repair of articular cartilage defects. But, the effect of low oxygen tension on the proliferation and chondrogenic differentiation in SDSCs has not characterized. In this study, we investigated the effects of hypoxia on proliferation and chondrogenesis in SDSCs. Method: SDSCs were isolated from patients with osteoarthritis at total knee replacement. To determine the effect of oxygen tension on proliferation and colony-forming characteristics of SDSCs, A colony-forming unit (CFU) assay and cell counting-based proliferation assay were performed under normoxic (21% oxygen) or hypoxic (5% oxygen). For in vitro chondrogenic differentiation, SDSCs were concentrated to form pellets and subjected to conditions appropriate for chondrogenic differentiation under normoxia and hypoxia, followed by the analysis for the expression of genes and proteins of chondrogenesis. qRT-PCR, histological assay, and glycosoaminoglycan assays were determined to assess chondrogenesis. Results: Low oxygen condition significantly increased proliferation and colony-forming characteristics of SDSCs compared to that of SDSCs under normoxic culture. Similar pellet size and weight were found for chondrogensis period under hypoxia and normoxia condition. The mRNA expression of types II collagen, aggrecan, and the transcription factor SOX9 was increased under hypoxia condition. Histological sections stained with Safranin-O demonstrated that hypoxic conditions had increased proteoglycan synthesis. Immunohistochemistry for types II collagen demonstrated that hypoxic culture of SDSCs increased type II collagen expression. In addition, GAG deposition was significantly higher in hypoxia compared with normoxia at 21 days of differentiation. Conclusion: These findings show that hypoxia condition has an important role in regulating the synthesis ECM matrix by SDSCs as they undergo chondrogenesis. This has important implications for cartilage tissue engineering applications of SDSCs.

• Ocean and Polar Research
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• v.44 no.1
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• pp.1-11
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• 2022

Hypoxia can affect water-atmosphere methane flux by controlling the production and consumption processes of methane in coastal areas. Seasonal methane concentration and fluxes were quantified to evaluate the effects of seasonal hypoxia in Dangdong Bay (Gyeongsangnamdo, Jinhae Bay, South Korea). Sediment-water methane flux increased more than 300 times during hypoxia (normoxia and hypoxia each 6, 1900 µmol m^-2 d^-1), and water-atmospheric methane flux and bottom methane concentration increased about 2, 10 times (normoxia and hypoxia each 190, 420 µmol m^-2 d^-1; normoxia and hypoxia each 22, 230 nM). Shoaling of anaerobic decomposition of organic matter in the sediments during the hypoxia (August) was confirmed by the change of the depth at which the maximum hydrogen sulfide concentration was detected. Shoaling shortens the distance between the water column and methanogenesis section to facilitate the inflow of organic matter, which can lead to an increase in methane production. In addition, since the transport distance of the generated methane to the water column is shortened, consumption of methane will be reduced. The combination of increased production and reduced consumption could increase sediment-aqueous methane flux and dissolved methane, which is thought to result in an increase in water-atmospheric methane flux. We could not observe the emission of methane accumulated during the hypoxia due to stratification, so it is possible that the estimated methane flux to the atmosphere was underestimated. In this study, the increase in methane flux in the coastal area due to hypoxia was confirmed, and the necessity of future methane production studies according to oxygen conditions in various coastal areas was demonstratedshown in the future.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.165-170
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• 2012

Cell migration plays a role in many physiological and pathological processes. Reactive oxygen species (ROS) produced in mammalian cells influence intracellular signaling processes which in turn regulate various biological activities. Here, we investigated whether melanoma cell migration could be controlled by ROS production under normoxia condition. Cell migration was measured by wound healing assay after scratching confluent monolayer of B16F10 mouse melanoma cells. Cell migration was enhanced over 12 h after scratching cells. In addition, we found that ROS production was increased by scratching cells. ERK phosphorylation was also increased by scratching cells but it was decreased by the treatment with ROS scavengers, N-acetylcysteine (NAC). Tumor cell migration was inhibited by the treatment with PD98059, ERK inhibitor, NAC or DPI, well-known ROS scavengers. Tumor cell growth as judged by succinate dehydrogenase activity was inhibited by NAC treatment. When mice were intraperitoneally administered with NAC, the intracellular ROS production was reduced in peripheral blood mononuclear cells. In addition, B16F10 tumor growth was significantly inhibited by in vivo treatment with NAC. Collectively, these findings suggest that tumor cell migration and growth could be controlled by ROS production and its downstream signaling pathways, in vitro and in vivo.

• BMB Reports
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• v.56 no.4
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• pp.252-257
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• 2023

The hypoxia-inducible factor-1α (HIF-1α) is a key regulator of hypoxic stress under physiological and pathological conditions. HIF-1α protein stability is tightly regulated by the ubiquitin-proteasome system (UPS) and autophagy in normoxia, hypoxia, and the tumor environment to mediate the hypoxic response. However, the mechanisms of how the UPS and autophagy interplay for HIF-1α proteostasis remain unclear. Here, we found a HIF-1α species propionylated at lysine (K) 709 by p300/CREB binding protein (CBP). HIF-1α stability and the choice of degradation pathway were affected by HIF-1α propionylation. K709-propionylation prevented HIF-1α from degradation through the UPS, while activated chaperon-mediated autophagy (CMA) induced the degradation of propionylated and nonpropionylated HIF-1α. CMA contributed to HIF-1α degradation in both normoxia and hypoxia. Furthermore, the pan-cancer analysis showed that CMA had a significant positive correlation with the hypoxic signatures, whereas SIRT1, responsible for K709-depropionylation correlated negatively with them. Altogether, our results revealed a novel mechanism of HIF-1α distribution into two different degradation pathways.

• Clinical and Experimental Pediatrics
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• v.53 no.10
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• pp.898-908
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• 2010

Purpose: The neuroprotective effects of erythropoietin (EPO) have been recently shown in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity; however, limited data are available for such effects during the neonatal periods. Therefore, we investigated whether recombinant human EPO (rHuEPO) can protect against perinatal HI brain injury via an antiapoptotic mechanism. Methods: The left carotid artery was ligated in 7-day-old Sprague-Dawley (SD) rat pups ($in$ $vivo$ model). The animals were divided into 6 groups: normoxia control (NC), normoxia sham-operated (NS), hypoxia only (H), hypoxia+vehicle (HV), hypoxia+rHuEPO before a hypoxic insult (HE-B), and hypoxia+rHuEPO after a hypoxic insult (HE-A). Embryonic cortical neuronal cell culture of SD rats at 18 days gestation ($in$ $vitro$ model) was performed. The cultured cells were divided into 5 groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated groups. Results: In the $in$ $vivo$ model, Bcl-2 expressions in the H and HV groups were lower than those in the NC and NS groups, whereas those in the HE-A and HE-B groups were greater than those of the H and HV groups. The expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were in contrast to those of Bcl-2. In the $in$ $vitro$ model, the patterns of Bcl-2, Bax, and caspase-3 expression and Bax/Bcl-2 ratio were similar to the results obtained in the in vivo model. Conclusion: rHuEPO exerts neuroprotective effect against perinatal HI brain injury via an antiapoptotic mechanism.

• Journal of Life Science
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• v.23 no.1
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• pp.131-136
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• 2013

Sirtuin proteins have emerged as important modulators of several age-associated diseases. These include cancer and diabetes, as well as cardiovascular and neurodegenerative diseases. Among the sirtuin family members, SIRT2 mRNA is strongly expressed. To investigate the pathophysiological significance of SIRT2 as a primary regulator of angiogenesis, we focused on the biological role of SIRT2 under hypoxic conditions, examining the gene expression pattern of sirtuin family members in human umbilical vein endothelial cells (HUVECs). SIRT2 was expressed primarily in the cytoplasm, but it was dynamically trans-localized in the nuclear by hypoxia stimuli. Interestingly, both SIRT2 and the pro-angiogenic factor, VEGF, were up- regulated by hypoxia. A Matrigel assay demonstrated that the HUVECs formed a tube-like structure under hypoxia. The SIRT2 inhibitor, AK-1, significantly decreased the tube-forming activity of the HUVECs under either normoxia or hypoxia conditions. These findings suggest that SIRT2 might be a key regulator of angiogenesis.

• Aerospace Engineering and Technology
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• v.8 no.1
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• pp.207-214
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• 2009

The purpose of this study was to examine the influence of hypoxic exercise at head down tilt (HDT) on cardiovascular responses. Eight men ($23{\pm}2$ yrs, $176{\pm}4$ cm, and $75{\pm}8$ kg) underwent four separate exercise testing sessions; seated normoxia (SN), seated hypoxia (SH), HDT normoxia (HN), and HDT hypoxia (HH). Each participant performed the leg cycling at predetermined 40% of maximal aerobic capacity relevant to each posture for 15 min. Heart rate was higher in SH than SN and higher also in HH than SH (p<0.05). Blood oxygen saturation was lower in SH than SN (p<0.05). During resting, diastolic blood pressure and mean arterial pressure was significantly lower in HDT than seated posture (p<0.05). No differences were found between conditions in hemoglobin and hematocrit and electrolytes including, sodium, potassium, and chloride. Lactate was higher in SH than SN. In conclusion, there was no effect for cardiovascular responses to duplicate stimuli both hypoxia and posture.