• Biomedical Science Letters
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• v.19 no.3
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• pp.180-187
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• 2013

Hypoxia is an integral part of the environment during luteolysis. In this study we examined whether hypoxia could directly stimulate endothelial cells to produce nitric oxide (NO). Endothelial cells were cultured in hypoxic (5% $O_2$) or normoxic (20% $O_2$) conditions and the levels of total NO, inducible NO and endothelial NO was measured. We found that hypoxia but not normoxia upregulated NO production. The increased NO levels correlated with increased inducible NO synthase (iNOS) expression whereas expression of endothelial NOS (eNOS) expression remained constant. Addition of the iNOS specific inhibitor 1400W to hypoxic cultures prevented NO production suggesting that hypoxia-induced NO production in endothelial cells was due mainly to upregulation of iNOS. We also found that prostaglandin $F_{2{\alpha}}$ (PGF) production was unaffected by hypoxia suggesting that upregulation of NO was not due to increased synthesis of PGF. In summary, we report that endothelial cells cultured under hypoxic conditions produce NO via the iNOS pathway. This study provides the importance of the relation between the hypoxic environment and the induction of NO by endothelial cells during regression of the corpus luteum in the ovary.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2031-2035
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• 2015

Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

• Journal of Ecology and Environment
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• v.43 no.3
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• pp.289-296
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• 2019

We investigated the mortality and the oxidative damages of Deschampsia antarctica in response to waterlogging stress. In field, we compared the changes in the density of D. antarctica tuft at the two different sites over 3 years. The soil water content at site 2 was 6-fold higher than that of site 1, and the density of D. antarctica tuft decreased significantly by 55.4% at site 2 for 3 years, but there was no significant change at site 1. Experimental results in growth chamber showed that the $H_2O_2$ and malondialdehyde content increased under root-flooding treatment (hypoxic conditions-deficiency of $O_2$), but any significant change was not perceptible under the shoot-flooding treatment (anoxic condition-absence of $O_2$). However, total chlorophyll, soluble sugar, protein content, and phenolic compound decreased under the shoot-flooding treatment. In addition, the catalase activity increased significantly on the 1st day of flooding. These results indicate that hypoxic conditions may lead to the overproduction of reactive oxygen species, and anoxic conditions can deplete primary metabolites such as sugars and protein in the leaf tissues of D. antarctica. Under present warming trend in Antarctic Peninsula, D. antarctica tuft growing near the shoreline might more frequently experience flooding due to glacier melting and inundation of seawater, which can enhance the risk of this plant mortality.

• 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.

• Journal of Environmental Science International
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• v.19 no.5
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• pp.607-615
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• 2010

We investigated the temporal variations of heterotrophic dinoflagellates (hereafter HDNF) and photosynthetic dinoflagellates (hereafter PDNF) from 14 June to 4 September 2003 at a single station in Jangmok Bay. We took water samples 47 times from 2 depths (surface and bottom layers) at hide tide. A total of 63 species were encountered and in general the most abundant genera were Prorocentrum and Protoperidinium. The abundance of PDNF and HDNF was in the range of $0.04{\sim}55.8{\times}10^4$ cells/L and in the range of $0.01{\sim}4.35{\times}10^4$ cells/L, respectively. The mean abundance of PDNF was approximately 7 times higher than that of HDNF, and was higher in the surface layer where has enough irradiance for photosynthesis than in the bottom layer. The total dinoflagellate abundance was higher in the NLP (nitrogen limitation period) than in the SLP (silicate limitation period), and the abundance in the hypoxic conditions was similar to that in the normal conditions. The Shannon-Weaver species diversity index were slightly higher in the bottom layer, the SLP and the hypoxic conditions. The PDNF abundance were correlated with temperature, DO, total inorganic nitrogen and phosphate in the whole water column, and the HDNF abundance was significantly correlated with temperature, salinity and DO. This study shows that the dinoflagellate abundance might be affected by abiotic factors such as irradiance, temperature, salinity, DO and the concentrations of inorganic nutrients, and provides baseline information for further studies on plankton dynamics in Jangmok Bay.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.27 no.2
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• pp.200-214
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• 1994

In order to clarify the benthic environmental properties as a part of a study on the macrobenthic community in the Chinhae Bay System, water temperature, salinity and dissolved oxygen (DO) in surface and bottom water layers, mean grain size (${\phi}$) and sediment organic carborn (SOC) in surface sediment were analyzed at twelve stations during the period from June 1987 to May 1990. A high sediment organic carbon and hypoxic condition in bottom water due to the development of summer stratification and fine sediment texture toward the inner bay were important environmental characteristics of Chinhae Bay. Hypoxic conditions began to develop in the inner bay from May, and gradually spread toward the outer bay in summer with a peak in September when half the bay was affected by this oxygen deficiency. Recovery from this hypoxic condition in the bottom layer was observed from the beginning of autumn together with a disappearance of the summer stratification. Principal component analyses were carried out from the following five environmental variables:mean water temperature, salinity, dissolved oxygen in the bottom layer and mean grain size, sediment organic carbon in surface sediment. The twelve stations were classified into four areal groups based on the analyses. The division of the areal groups had high correlations to the sediment organic carbon content.

• Journal of the Korean Society of Marine Environment & Safety
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• v.27 no.6
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• pp.708-720
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• 2021

As hypoxia adversely affects the marine environment in northwestern Gamak Bay every summer, the present study determined its comprehensive occurrence mechanisms using the Multiple Regression Analysis (MRA) and suggested management directions based on the primary MRA factors. The first hypoxia occurred by thermocline related to weather conditions, with organic matter deposited inside the bay on 26^th June, 2017. Additionally, on 12^th July, halocline was also developed by increased rainfall, and the hypoxia was most expanded horizontally and vertically. The primary factors were the stratification and deposited organic matter. In contrast, the hypoxia correlated to phytoplankton growth and deposited organic matter on 8^th August was diminished with remarkably less precipitation. However, the stable halocline was caused by massive precipitation, and the reproduced phytoplankton re-generated the expanded hypoxia on 16^th August despite a short sampling interval. Subsequently, the hypoxia influenced by the deposited organic matter spread shallowly along the seafloor on 13^th September as the extinction period. These results suggest that stratification alleviation technologies, and the improvement and removal of the organic matter deposited on the surface sediment are necessary.

• Asian-Australasian Journal of Animal Sciences
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• v.12 no.2
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• pp.189-191
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• 1999

Mineral profile of serum and cerebrospinal fluid (CSF) of 15 Himalayan Yak (adult female, n=8; adult male n=4 and young male,n=3) was studied in their natural habitat at an altitude of 3300 meters above mean sea level at Sangla in north western Himalayas. The macro and micro minerals estimated in serum and CSF were; Sodium, Potassium, Calcium and Magnesium and Zinc, Copper and Iron respectively. The values recorded among different Yak groups did not significantly differ from each other except serum iron and haemoglobin which were significantly higher (p<0.05 ) in young male Yaks compared to the adult male and female Yaks. An observation of great significance was considerably higher potassium and lower sodium level in Yaks compared to other bovine species of plains. The serum potassium values in some adult female Yaks were recorded as high as 10.4 mEq/l and the values varied between 6.6 to 9.8 mEq/l in young male Yaks. The serum Sodium values and Na:K ratios in Yak serum ranged between 117.5 to 122.6 mEq/l and 13.7 to 15.3 respectively. The possible relationship of high serum Potassium value with hypoxic conditions and hostile mountain environment has been discussed.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.53-62
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• 2016

Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride ($CoCl_2$) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of $CoCl_2$ preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. $CoCl_2$ treatment of MSCs markedly increased HIF-$1{\alpha}$ and VEGF mRNA, and protein expression of HIF-$1{\alpha}$. Temporary preconditioning of MSCs with $CoCl_2$ induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. $CoCl_2$ also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. $CoCl_2$ suppressed the expression of adipogenic markers including $PPAR{\gamma}$, aP2, and $C/EBP{\alpha}$, and inhibited adipogenesis. Temporary preconditioning with $CoCl_2$ could affect the multi-lineage differentiation of MSCs.

• BMB Reports
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• v.51 no.4
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• pp.174-181
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• 2018

A number of genes have been therapeutically targeted to relieve cancer, but cancer relapse is still a growing issue. The concept that the surrounding tumor environment is critical for the progression of cancer may foster an answer to the issue of cancer malignancy. Runt domain transcription factors (RUNX1, 2, and 3) are evolutionarily conserved and have been intensively studied for their roles in normal development and pathological conditions. During tumor growth, a hypoxic microenvironment and infiltration of the tumor by immune cells are common phenomena. In this review, we briefly introduce the consequences of hypoxia and immune cell infiltration into the tumor microenvironment with a focus on RUNX3 as a critical regulator. Furthermore, based on our current knowledge of the functional role of RUNX3 in hypoxia and immune cell maintenance, a probable therapeutic intervention is suggested for the effective management of tumor growth and malignancy.