• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.645-650
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• 2019

Brown adipocytes have an important role in the regulation of energy balance through uncoupling protein-1 (UCP-1)-mediated nonshivering thermogenesis. Although brown adipocytes have been highlighted as a new therapeutic target for the treatment of metabolic diseases, such as obesity and type II diabetes in adult humans, the molecular mechanism underlying brown adipogenesis is not fully understood. We recently found that protein tyrosine phosphatase receptor type B (PTPRB) expression dramatically decreased during brown adipogenic differentiation. In this study, we investigated the functional roles of PTPRB and its regulatory mechanism during brown adipocyte differentiation. Ectopic expression of PTPRB led to a reduced brown adipocyte differentiation by suppressing the tyrosine phosphorylation of VEGFR2, whereas a catalytic inactive PTPRB mutant showed no effects on differentiation and phosphorylation. Consistently, the expression of brown adipocyte-related genes, such as UCP-1, $PGC-1{\alpha}$, PRDM16, $PPAR-{\gamma}$, and CIDEA, were significantly inhibited by PTPRB overexpression. Overall, these results suggest that PTPRB functions as a negative regulator of brown adipocyte differentiation through its phosphatase activity-dependent mechanism and may be used as a target protein for the regulation of obesity and type II diabetes.

• Journal of Digital Convergence
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• v.16 no.12
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• pp.343-349
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• 2018

Electroencephalograph(EEG) information, which is an important data of brain science, reflects various levels of information from the molecular level to the behavior and cognitive stages, and the explosively amplified information is provided at each stage. Therefore, EEG information is an intrinsic privacy area of an individual, which is important information to be protected. In this paper, we apply spring security to web based system of spring MVC (Model, View, Control) framework to build independent and lightweight server system with powerful security system. Through the proposal of the platform type EEG analysis system which enhances the security function, the web service security of the EEG information is enhanced and the privacy of the EEG information can be protected.

• Molecules and Cells
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• v.42 no.2
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• pp.135-142
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• 2019

OCT4, also known as POU5F1 (POU domain class 5 transcription factor 1), is a transcription factor that acts as a master regulator of pluripotency in embryonic stem cells and is one of the reprogramming factors required for generating induced pluripotent stem cells. The human OCT4 encodes three isoforms, OCT4A, OCT4B, and OCT4B1, which are generated by alternative splicing. Currently, the functions and expression patterns of OCT4B remain largely unknown in malignancies, especially in human glioblastomas. Here, we demonstrated the function of OCT4B in human glioblastomas. Among the isoform of OCT4B, OCT4B-190 ($OCT4B^{19kDa}$) was highly expressed in human glioblastoma stem cells and glioblastoma cells and was mainly detected in the cytoplasm rather than the nucleus. Overexpression of $OCT4B^{19kDa}$ promoted colony formation of glioblastoma cells when grown in soft agar culture conditions. Clinical data analysis revealed that patients with gliomas that expressed OCT4B at high levels had a poorer prognosis than patients with gliomas that expressed OCT4B at low levels. Thus, $OCT4B^{19kDa}$ may play a crucial role in regulating cancer cell survival and adaption in a rigid environment.

• Molecules and Cells
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• v.42 no.2
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• pp.143-150
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• 2019

Chronic neuropathic pain is one of the primary causes of disability subsequent to spinal cord injury. Patients experiencing neuropathic pain after spinal cord injury suffer from poor quality of life, so complementary therapy is seriously needed. Dehydrocorybulbine is an alkaloid extracted from Corydalis yanhusuo. It effectively alleviates neuropathic pain. In the present study, we explored the effect of dehydrocorybulbine on neuropathic pain after spinal cord injury and delineated its possible mechanism. Experiments were performed in rats to evaluate the contribution of dehydrocorybulbine to P2X4 signaling in the modulation of pain-related behaviors and the levels of pronociceptive interleukins and proteins after spinal cord injury. In a rat contusion injury model, we confirmed that chronic neuropathic pain is present on day 7 after spinal cord injury and P2X4R expression is exacerbated after spinal cord injury. We also found that administration of dehydrocorybulbine by tail vein injection relieved pain behaviors in rat contusion injury models without affecting motor functions. The elevation in the levels of pronociceptive interleukins ($IL-1{\beta}$, IL-18, MMP-9) after spinal cord injury was mitigated by dehydrocorybulbine. Dehydrocorybulbine significantly mitigated the upregulation of P2X4 receptor and reduced ATP-evoked intracellular $Ca^{2+}$ concentration. Both P2XR and dopamine receptor2 agonists antagonized dehydrocorybulbine's antinociceptive effects. In conclusion, we propose that dehydrocorybulbine produces antinociceptive effects in spinal cord injury models by inhibiting P2X4R.

• Korean Journal of Agricultural Science
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• v.45 no.4
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• pp.635-643
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• 2018

Bovine milk is widely consumed by humans and is a primary ingredient of dairy foods. Proteomic approaches have the potential to elucidate complex milk proteins and have been used to study milk of various species. Here, we performed a proteomic analysis using 2-dimensional electrophoresis (2-DE) and matrix assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF MS) to identify whey proteins in bovine milk obtained soon after parturition (bovine early milk). The major casein proteins were removed, and the whey proteins were analyzed with 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The whey proteins (2 mg) were separated by pI and molecular weight across pH ranges of 3.0 - 10.0 and 4.0 - 7.0. The 2-DE gels held about 300 to 700 detectable protein spots. We randomly picked 12 and nine spots that were consistently expressed in the pH 3.0 - 10.0 and pH 4.0 - 7.0 ranges, respectively. Following MALDI-TOF MS analysis, the 21 randomly selected proteins included proteins known to be present in bovine milk, such as albumin, lactoferrin, serum albumin precursor, T cell receptor, polymeric immunoglobulin receptor, pancreatic trypsin inhibitor, aldehyde oxidase and microglobulin. These proteins have major functions in immune responses, metabolism and protein binding. In summary, we herein identified both known and novel whey proteins present in bovine early milk, and our sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed their expression pattern.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.10
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• pp.1483-1490
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• 2019

Objective: To explore the molecular mechanisms of fat metabolism and deposition in pigs, an experiment was conducted to identify hepatic mRNAs and miRNAs expression and determine the potential interaction of them in two phenotypically extreme pig breeds. Methods: mRNA and miRNA profiling of liver from 70-day Jinhua (JH) and Landrace (LD) pigs were performed using RNA sequencing. Blood samples were taken to detect results of serum biochemistry. Bioinformatics analysis were applied to construct differentially expressed miRNA-mRNA network. Results: Serum total triiodothyronine and total thyroxine were significantly lower in Jinhua pigs, but the content of serum total cholesterol (TCH) and low-density lipoprotein cholesterol were strikingly higher. A total of 467 differentially expressed genes (DEGs) and 35 differentially expressed miRNAs (DE miRNAs) were identified between JH and LD groups. Gene ontology analysis suggested that DEGs were involved in oxidation-reduction, lipid biosynthetic and lipid metabolism process. Interaction network of DEGs and DE miRNAs were constructed, according to target prediction results. Conclusion: We generated transcriptome and miRNAome profiles of liver from JH and LD pig breeds which represent distinguishing phenotypes of growth and metabolism. The potential miRNA-mRNA interaction networks may provide a comprehensive understanding in the mechanism of lipid metabolism. These results serve as a basis for further investigation on biological functions of miRNAs in the porcine liver.

• Molecules and Cells
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• v.42 no.1
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• pp.87-95
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• 2019

Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

• Molecules and Cells
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• v.42 no.5
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• pp.406-417
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• 2019

RICE FLOWERING LOCUS T 1 (RFT1) is a major florigen that functions to induce reproductive development in the shoot apical meristem (SAM). To further our study of RFT1, we overexpressed the gene and examined the expression patterns of major regulatory genes during floral transition and inflorescence development. Overexpression induced extremely early flowering in the transgenics, and a majority of those calli directly formed spikelets with a few spikelets, thus bypassing normal vegetative development. FRUITFULL (FUL)-clade genes OsMADS14, OsMADS15, and OsMADS18 were highly induced in the RFT1-expressing meristems. OsMADS34 was also induced in the meristems. This indicated that RFT1 promotes the expression of major regulatory genes that are important for inflorescence development. RFT1 overexpression also induced SEPALLATA (SEP)-clade genes OsMADS1, OsMADS5, and OsMADS7 in the greening calli before floral transition occurred. This suggested their possible roles at the early reproductive stages. We found it interesting that expression of OsFD1 as well as OsFD2 and OsFD3 was strongly increased in the RFT1-expressing calli and spikelets. At a low frequency, those calli produced plants with a few leaves that generated a panicle with a small number of spikelets. In the transgenic leaves, the FUL-clade genes and OsMADS34 were induced, but SEP-clade gene expression was not increased. This indicated that OsMADS14, OsMADS15, OsMADS18, and OsMADS34 act immediately downstream of RFT1.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.395-401
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• 2021

Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E₂ (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.

• Molecules and Cells
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• v.44 no.2
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• pp.101-115
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• 2021

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression. However, the E3 ubiquitin ligase that targets Ino80 for proteasomal degradation was unknown. Here, we identified the C-terminus of Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase that functions in cooperation with Hsp70, as an Ino80-interacting protein. CHIP polyubiquitinates Ino80 in a manner dependent on Hsp70. Contrary to our expectation that CHIP degrades Ino80, CHIP instead stabilizes Ino80 by extending its half-life. The data suggest that CHIP stabilizes Ino80 by inhibiting degradative ubiquitination. We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding. Interestingly, both depletion and overexpression of CHIP compromise replication fork progression with little effect on fork stalling, as similarly observed for BAP1 and Ino80, indicating that an optimal cellular level of Ino80 is important for replication fork speed but not for replication stress suppression. This work therefore idenitifes CHIP as an E3 ubiquitin ligase that stabilizes Ino80 via nondegradative ubiquitination and suggests that CHIP and BAP1 act in concert to regulate Ino80 ubiquitination to fine-tune its stability for efficient DNA replication.