• Molecules and Cells
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• v.37 no.4
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• pp.345-355
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• 2014

Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing ($GFAP^+$) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, $GFAP^+$ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including $S100{\beta}$, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.

• Journal of Embryo Transfer
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• v.29 no.4
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• pp.375-383
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• 2014

Klotho (KL) is a single transmembrane protein composed of KL1 and KL2 repeats possessing ${\beta}$-glucuronidase activity and maintains calcium homeostasis in physiological state. It has been implicated in pigs that calcium is important for the establishment and maintenance of pregnancy, and our previous study has shown that transient receptor potential vanilloid type 6 (TRPV6), a calcium ion transporter, is predominantly expressed in the uterine endometrium during pregnancy in pigs. However, expression and function of KL in the uterine endometrium has not been determined in pigs. Thus, the present study determined expression and regulation of KL in the uterine endometrium during the estrous cycle and pregnancy in pigs. Real-time RT-PCR analysis showed that levels of KL mRNA decreased between Days 12 to 15 of the estrous cycle, and its expression showed a biphasic manner during pregnancy. KL mRNA was expressed in conceptuses and in chorioallantoic tissues during pregnancy. Explant culture study showed that expression levels of KL were not affected by treatment of steroid hormones or interleukin-1beta during the implantation period. Furthermore, levels of KL mRNA in the uterine endometrium from gilts carrying somatic cell nuclear transfer (SCNT)-derived embryos were significantly lower than those from gilts carrying natural mating-derived embryos on Day 12 of pregnancy. These results exhibited that KL was expressed at the maternal-conceptus interface in a pregnancy status- and stage-specific manner, and its expression was affected by SCNT procedure, suggesting that KL may play an important role in the establishment and maintenance of pregnancy in pigs.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.293-298
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• 2012

The purpose of this study was to investigate the modification of expression and functionality of the drug transporter P-glycoprotein (P-gp) by tumor necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) at the blood-brain barrier (BBB). We used immortalized human brain microvessel endothelial cells (iHBMEC) and primary human brain microvessel endothelial cells (pHBMEC) as in vitro BBB model. To investigate the change of p-gp expression, we carried out real time PCR analysis and Western blotting. To test the change of p-gp activity, we performed rhodamin123 (Rh123) accumulation study in the cells. In results of real time PCR analysis, the P-gp mRNA expression was increased by TNF-${\alpha}$ or IFN-${\gamma}$ treatment for 24 hr in both cell types. However, 48 hr treatment of TNF-${\alpha}$ or IFN-${\gamma}$ did not affect P-gp mRNA expression. In addition, co-treatment of TNF-${\alpha}$ and IFN-${\gamma}$ markedly increased the P-gp mRNA expression in both cells. TNF-${\alpha}$ or IFN-${\gamma}$ did not influence P-gp protein expression whatever the concentration of cytokines or duration of treatment in both cells. However, P-gp expression was increased after treatments of both cytokines together in iHBMEC cells only compared with untreated control. Furthermore, in both cell lines, TNF-${\alpha}$ or IFN-${\gamma}$ induced significant decrease of P-gp activity for 24 hr treatment. And, both cytokines combination treatment also decreased significantly P-gp activity. These results suggest that P-gp expression and function at the BBB is modulated by TNF-${\alpha}$ or/and IFN-${\gamma}$. Therefore, the distribution of P-gp depending drugs in the central nervous system can be modulated by neurological inflammatory diseases.

• Journal of Plant Biotechnology
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• v.37 no.4
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• pp.483-493
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• 2010

Knock-out of a gene by insertional mutagenesis is a direct way to address its function through the mutant phenotype. Among ca. 15,000 gene-trapped Ds insertion lines of rice, we identified one line from selected sensitive lines in highly salt stress. We conducted gene tagging by TAIL-PCR, and DNA gel blot analysis from salt sensitive mutant. A gene encoding an oligopeptide transporter (OPT family) homologue was disrupted by the insertion of a Ds transposon into the OsOPT10 gene that was located shot arm of chromosome 8. The OsOPT10 gene (NP_001062118.) has 6 exons and encodes a protein (752 aa) containing the OPT family domain. RT-PCR analysis showed that the expression of OsOPT10 gene was rapidly and strongly induced by stresses such as high-salinity (250 mM), osmotic, drought, $100\;{\mu}M$ ABA. The subcellular localization assay indicated that OsOPT10 was localized specifically in the plasma membrane. Overexpression of OsOPT10 in Arabidopsis thaliana and rice conferred tolerance of transgenic plants to salt stress. Further we found expression levels of some stress related genes were inhibited in OsOPT10 transgenic plants. These results suggested that OsOPT10 might play crucial but differential roles in plant responses to various abiotic stresses.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1146-1150
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• 2008

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.2
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• pp.83-92
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• 2009

This study was undertaken to examine the effect of oxidants on membrane transport function in renal epithelial cells. Hydrogen peroxide ($H_2O_2$) was used as a model oxidant and the membrane transport function was evaluated by measuring $Na^+$-dependent phosphate ($Na^+$-Pi) uptake in opossum kidney (OK) cells. $H_2O_2$ inhibited $Na^+$-Pi uptake in a dose-dependent manner. The oxidant also caused loss of cell viability in a dose-dependent fashion. However, the extent of inhibition of the uptake was larger than that in cell viability. $H_2O_2$ inhibited $Na^+$-dependent uptake without any effect on $Na^+$-independent uptake. $H_2O_2$-induced inhibition of $Na^+$-Pi uptake was prevented completely by catalase, dimethylthiourea, and deferoxamine, suggesting involvement of hydroxyl radical generated by an iron-dependent mechanism. In contrast, antioxidants Trolox, N,N'-diphenyl-p-phenylenediamine, and butylated hydroxyanisole did not affect the $H_2O_2$ inhibition. Kinetic analysis indicated that $H_2O_2$ decreased Vmax of $Na^+$-Pi uptake with no change in the Km value. Phosphonoformic acid binding assay did not show any difference between control and $H_2O_2$-treated cells. $H_2O_2$ also did not cause degradation of $Na^+$-Pi transporter protein. Reduction in $Na^+$-Pi uptake by $H_2O_2$ was associated with ATP depletion and direct inhibition of $Na^+$-$K^+$-ATPase activity. These results indicate that the effect of $H_2O_2$ on membrane transport function in OK cells is associated with reduction in functional $Na^+$-pump activity. In addition, the inhibitory effect of $H_2O_2$ was not associated with lipid peroxidation.

• Clinical and Experimental Pediatrics
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• v.64 no.11
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• pp.559-572
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• 2021

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%-10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2-3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1-2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.

• BMB Reports
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• v.52 no.7
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• pp.457-462
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• 2019

[18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value ($SUV_{max}$), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.12
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• pp.1852-1862
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• 2018

Objective: The purpose of this study was to investigate a single step genome-wide association study (ssGWAS) for identifying genomic regions affecting reproductive traits in Landrace and Large White pigs. Methods: The traits included the number of pigs weaned per sow per year (PWSY), the number of litters per sow per year (LSY), pigs weaned per litters (PWL), born alive per litters (BAL), non-productive day (NPD) and wean to conception interval per litters (W2CL). A total of 321 animals (140 Landrace and 181 Large White pigs) were genotyped with the Illumina Porcine SNP 60k BeadChip, containing 61,177 single nucleotide polymorphisms (SNPs), while multiple traits single-step genomic BLUP method was used to calculate variances of 5 SNP windows for 11,048 Landrace and 13,985 Large White data records. Results: The outcome of ssGWAS on the reproductive traits identified twenty-five and twenty-two SNPs associated with reproductive traits in Landrace and Large White, respectively. Three known genes were identified to be candidate genes in Landrace pigs including retinol binding protein 7, and ubiquitination factor E4B genes for PWL, BAL, W2CL, and PWSY and one gene, solute carrier organic anion transporter family member 6A1, for LSY and NPD. Meanwhile, five genes were identified to be candidate genes in Large White, two of which, aldehyde dehydrogenase 1 family member A3 and leucine rich repeat kinase 1, associated with all of six reproduction traits and three genes; retrotransposon Gag like 4, transient receptor potential cation channel subfamily C member 5, and LHFPL tetraspan subfamily member 1 for five traits except W2CL. Conclusion: The genomic regions identified in this study provided a start-up point for marker assisted selection and estimating genomic breeding values for improving reproductive traits in commercial pig populations.

• BMB Reports
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• v.54 no.6
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• pp.323-328
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• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.