• Journal of Animal Science and Technology
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• v.50 no.1
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• pp.45-56
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• 2008

In the present study, real-time PCR was performed to evaluated expression of several isoforms of monocarboxylate transporters(MCTs) and two known MCT regulatory proteins, basigin (Bsg) and embigin, in the epididymis of the male reproductive tract during postnatal development. In addition, ERα�-mediated regulation of MCT1 expression in the epididymis was determined with estrogen receptor(ER) α� knockout(α�ERKO) mice by immunohistochemistry. Results from the current study demonstrated differential expression of MCT isoform(MCT 1, 2, 3, 4, and 8), Bsg, and embigin mRNAs in rat epididymis according to postnatal age and epididymal region. In addition, immunohistochemical study of MCT1 revealed the limited localization of MCT1 at apical area of corpus and caudal epididymis. The present study also showed that expression of MCT1 was not directly regulated by ERα�. The findings from the current study suggest that MCTs would involve in establishing adequate microenvironment for sperm maturation and storage in the epididymis, eventually leading to maintenance of male fertility.

• Journal of Animal Science and Technology
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• v.49 no.3
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• pp.309-320
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• 2007

The purpose of the present study was to determine if monocarboxylate transporter(MCT) isoforms and Basigin(Bsg) are expressed in the efferent ductules(ED) and if MCT1 expression is under estrogen receptor(ER)α-regulation in the ED of male reproductive tract. The presence of MCT isoforms and Bsg mRNAs was detected by real-time polymerization chain reaction(PCR), and ERα-mediated regulation of MCT1 expression in the ED was indirectly determined by immuno- histochemistry. Current study found differential expression of MCT isoforms(MCT1, 2, 3, 4, and 8) and Bsg mRNAs in rat ED according to postnatal ages. In addition, comparison of MCT1 expression in the ED between wild type and ERα knockout mice at different postnatal ages showed basolateral localization of MCT1 in ciliated cells of the ED and, in part, ERα- mediated regulation of MCT1 expression. It is suggested that MCTs would play a role in regulation of function of the ED.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8923-8929
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• 2014

Background: Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC. Materials and Methods: Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data. Results: High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value. Conclusions: These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.

• Physical Therapy Rehabilitation Science
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• v.10 no.2
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• pp.175-184
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• 2021

Objective: Fatigue can decrease both quality of life and work efficiency. Ginseng is one of the most popular herbal treatments for improving personal health, with applications in treating fatigue. However, the exact mechanisms of anti-fatigue effects are still unclear. Thus, we investigated the effect of red ginseng powder (RGP) on exercise capacity and peripheral fatigue using both behavioral and molecular experiments in mice. Design: Four-groups behavioral and molecular experiment. Methods: Male 6-weeks-old ICR mice were treated with distilled water, 100, and 200 mg/kg RGP for 5 days via oral administration. The exercise capacity of each animal group was measured by locomotor activity, rota-rod, hanging wire, and cold swimming tests. Additionally, after performing the treadmill to induce fatigue, lactate expression and molecular experiments were investigated using mice gastrocnemius. Results: Mice treated with RGP exhibited increased exercise capacity in the behavioral tests. Additionally, RGP induced a dose-dependent decrease in lactate levels after high-intensity exercise, and Monocarboxylate transporter (MCT) 4 expression increased in groups treated with RGP. However, there was no significant change in MCT1. Conclusions: These results suggest that RGP exerts several anti-fatigue properties by lower lactate and improved exercise capacity. Increased MCT4 expression may also affect lactate transport. Thus, this study suggests that the anti-fatigue properties of RGP might be associated with MCT4 activity.

• Journal of Korean Traditional Oncology
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• v.20 no.1
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• pp.81-88
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• 2015

Generally, normal cells synthesize adenosine triphosphate (ATP) through oxidative phosphorylation in the mitochondria. However, they produce ATP through lactic acid fermentation on hypoxic condition. Interestingly, many cancer cells rely on aerobic glycolysis for ATP generation instead of mitochondrial oxidative phosphorylation, which is termed as "Warburg effect". According to results from recent researches on differences of cancer cell metabolism from normal cell metabolism and because chemotherapy to suppress rapidly growing cells, as a side effect of cancer treatment, can still target healthy cells, there is merit in the development of small-molecule inhibitors targeting metabolic enzymes such as pyruvate dehydrogenase kinase (PDHK), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT). For new anticancer therapy, in this review, we show recent advances in study on cancer cell metabolism and molecules targeting metabolic enzymes which are importantly associated with cancer metabolism for cancer therapy. Furthermore, we would also like to emphasize the necessity of development of molecules targeting metabolic enzymes using herbal medicines and their constituents for anticancer drugs.

• Development and Reproduction
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• v.12 no.1
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• pp.19-30
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• 2008

Proper development of fertilized oocyte to blastocyst is a key step in mammalian development to implantation. During development of preimplantation embryos, the mammalian embryo needs supply the energy substrate for keep viability. Usually mammalian oocyte get substrate especially energy substrate from oviduct and uterus, because it does not store much substrate into cytoplasm during oogenesis. Carbohydrates are known as a main energy substrate for preimplantation stage embryos. Glucose, lactate and pyruvate are essential component in preimplantation embryo culture media and there are stage specific preferences to them. Glucose transporter and $H^+$-monocarboxylate cotransporter are a main mediator for carbohydrate transport and those expression levels are primarily under the control of intrinsic or extrinsic factors like insulin and glucose. Other organic substances, amino acids, lipids and nucleotides are used as energy substance and cellular regulation factor. Though since 1960s, successful development of fertilized embryo to blastocyst has been accomplished with chemically defined medium for example BWW and give rise to normal offspring in mammals, the role of metabolites and the regulation of intermediary metabolism are still poorly understood. Glucose may permit expression of metabolic enzymes and transporters in compacting morula, capable of generating the energy required for blastocyst formation. In addition, it has been suggested that the cytokines can modulate the metabolic rate of carbohydrate in embryos and regulate the preimplantation embryonic development through control the metabolic rate. Recently we showed that lactate can be used as a mediator for preimplantation embryonic development. Those observations indicate that metabolites of carbohydrate are required by the early embryo, not only as an energy source, but also as a key substrate for other regulatory and biosynthetic pathways. In addition metabolites of carbohydrate may involve in cellular activity during development of preimplantation embryos. It is suggested that through these regulation and with other regulation mechanisms, embryo and uterus can prepare the embryo implantation and further development, properly.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.307-318
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• 1988

Properties of succinate transport were examined in basolaterat membrane vesicles (BLMV) isolated from rabbit renal cortex. An inwardly directed $Na^+$ gradient stimulated succinate uptake and led to a transient overshoot. $K^+,{\;}Li^+,{\;}Rb^+$ and choline could not substitute for $Na^+$ in the uptake process. The dependence of the initial uptake rate of succinate on $Na^+$ concentration exhibited sigmoidal kinetics, indicating interaction of more than one $Na^+$ with transporter Hill coefficient for $Na^+$ was calculated to be 2.0. The $Na^+-dependent$ succinate uptake was electrogenic, resulting in the transfer of positive charge across the membrane. The succinate uptake into BLMV showed a pH optimum at external pH $7.5{\sim}8.0$, whereas succinate uptake into brush border membrane vesicles (BBMV) did not depend on external pH. Kinetic analysis showed that a Na-dependent succinate uptake in BLMV occurred via a single transport system, with an apparent Km of $15.5{\pm}0.94{\;}{\mu}M$ and Vmax of $16.22{\pm}0.25{\;}nmole/mg{\;}protein/min$. Succinate uptake was strongly inhibited by $4{\sim}5$ carbon dicarboxylates, whereas monocarboxylates and other organic anions showed a little or no effect. The succinate transport system preferred dicarboxylates in trans-configuration (furmarate) over cis-dicarboxylates (maleate). Succinate uptake was inhibited by the anion transport inhibitors DIDS, SITS and furosemide, and $Na^+-coupled$ transport inhibitor harmaline. These results indicate the existence of a $Na^+-dependent$ succinate transport system in BLMV that may be shared by the other Krebs cycle intemediates. This transport system seems to be very similar to the luminal transport system for dicarboxylates.

• Journal of Life Science
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• v.29 no.11
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• pp.1179-1191
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• 2019

Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.