• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.589-594
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• 2016

Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-${\beta}E$ in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-${\beta}E$ subunit of the TGF-${\beta}$ family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.

• Bioinformatics and Biosystems
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• v.2 no.1
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• pp.28-32
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• 2007

The protein phosphorylation is one of the important processes in the cell signaling pathway. A variety of protein kinase families are involved in this process, and each kinase family phosphorylates different kinds of substrate proteins. Many methods to predict the kinase-specific phosphoryrated sites or different types of phosphorylated residues (Serine/Threonine or Tyrosin) have been developed. We employed Supprot Vector Machine (SVM) to attempt the prediction of protein kinase specific phosphorylation sites. 10 different kinds of protein kinase families (PKA, PKC, CK2, CDK, CaM-KII, PKB, MAPK, EGFR) were considered in this study. We defined 9 residues around a phosphorylated residue as a deterministic instance from which protein kinases determine whether they act on. The subsets of PSI-BALST profile was converted to the numerical vectors to represent positive or negative instances. When SVM training, We took advantage of multiple SVMs because of the unbalanced training sets. Representative negative instances were drawn multiple times, and generated new traing sets with the same positive instances in the original traing set. When testing, the final decisions were made by the votes of those multiple SVMs. Generally, RBF kernel was used for the SVMs, and several parameters such as gamma and cost factor were tested. Our approach achieved more than 90% specificity throughout the protein kinase families, while the sensitivities recorded 60% on average.

• Molecules and Cells
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• v.40 no.5
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• pp.315-321
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• 2017

The inositol polyphosphates are a group of multifunctional signaling metabolites whose synthesis is catalyzed by a family of inositol kinases that are evolutionarily conserved from yeast to humans. Inositol polyphosphate multikinase (IPMK) was first identified as a subunit of the arginine-responsive transcription complex in budding yeast. In addition to its role in the production of inositol tetrakis- and pentakisphosphates ($IP_4$ and $IP_5$), IPMK also exhibits phosphatidylinositol 3-kinase (PI3-kinase) activity. Through its PI3-kinase activity, IPMK activates Akt/PKB and its downstream signaling pathways. IPMK also regulates several protein targets non-catalytically via protein-protein interactions. These non-catalytic targets include cytosolic signaling factors and transcription factors in the nucleus. In this review, we highlight the many known functions of mammalian IPMK in controlling cellular signaling networks and discuss future challenges related to clarifying the unknown roles IPMK plays in physiology and disease.

• International Journal of Oral Biology
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• v.44 no.2
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• pp.43-49
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• 2019

Tannic acid (TA) is a water-soluble polyphenol compound found in various herbal plants. We investigated the chemopreventive effects of TA on FaDu hypopharyngeal squamous carcinoma cells. In an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TA showed dose-dependent cytotoxicity with a half maximal inhibitory concentration (IC50) of 50 ?M. Cell cycle analysis and immunofluorescence imaging demonstrated that under low-dose ($25{\mu}M$) treatment, FaDu cells were arrested in G2/M phase, and as the dose of TA was increased, apoptosis was induced with the increase of cell population at sub-G1 phase. The expressions of various cyclins, including cyclin D1 and cyclin-dependent kinases (CDK-1 and CDK-2), were down-regulated at low doses of TA, whereas apoptotic effectors such as cleaved caspase 3, cleaved caspase 7, and poly (ADP-ribose) polymerase (PARP) were expressed in a dose-dependent manner in Western blotting. In addition, TA-induced apoptosis of FaDu cells might be mediated by the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase pathway, with the upregulation of p-AKT/p-PKB (phosphorylated protein kinase B) and p-ERK. Overall, our data support the hypothesis that TA is a potential candidate agent for the treatment of hypopharyngeal cancer.

• BMB Reports
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• v.54 no.9
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• pp.451-457
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• 2021

Over the last decades, research has focused on the role of pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPPs) in regulating cellular signaling via PI3K/Akt inhibition. The PKB/Akt signaling imbalances are associated with a variety of illnesses, including various types of cancer, inflammatory response, insulin resistance, and diabetes, demonstrating the relevance of PHLPPs in the prevention of diseases. Furthermore, identification of novel substrates of PHLPPs unveils their role as a critical mediator in various cellular processes. Recently, researchers have explored the increasing complexity of signaling networks involving PHLPPs whereby relevant information of PHLPPs in metabolic diseases was obtained. In this review, we discuss the current knowledge of PHLPPs on the well-known substrates and metabolic regulation, especially in liver, pancreatic beta cell, adipose tissue, and skeletal muscle in relation with the stated diseases. Understanding the context-dependent functions of PHLPPs can lead to a promising treatment strategy for several kinds of metabolic diseases.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.224-229
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• 2008

Eucommia ulmoides (Duchung) is commonly used for treatment of diabetes in Korean traditional medicine. However, the exact mechanism of its anti-diabetic effect has not yet been fully elucidated. In this study, the effect of E. ulmoides extract on glucose uptake was investigated in L6 rat skeletal muscle cells. E. ulmoides extract stimulated the activity of phosphatidylinositol (PI) 3-kinase that is a major regulatory molecule in glucose uptake pathway. Protein kinase B (PKB) and protein kinase C-${\xi}$ (PKC-${\xi}$), downstream mediators of PI 3-kinase, were also activated by E. ulmoides extract. We assessed the activity of AMP-activated protein kinase (AMPK), another regulatory molecule in glucose uptake pathway. Phosphorylation level of AMPK did not change with treatment of E. ulmoides extract. Phosphorylations of p38 mitogen activated protein kinase (p38 MAPK) and acetyl-CoA carboxylase (ACC), downstream mediators of AMPK, were not significantly different. Taken together, our results suggest that E. ulmoides may stimulate glucose uptake through PI 3-kinase but not AMPK in L6 skeletal muscle cells.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.38-43
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• 2020

Hand, foot, and mouth disease (HFMD) is caused by enterovirus 71 (EV71) in infants and children under six years of age. HFMD is characterized by fever, mouth ulcers, and vesicular rashes on the palms and feet. EV71 also causes severe neurological manifestations, such as brainstem encephalitis and aseptic meningitis. Recently, frequent outbreaks of EV71 have occurred in the Asia-Pacific region, but currently, no effective antiviral drugs have been developed to treat the disease. In this study, we investigated the antiviral effect of salvianolic acid B (SalB) on EV71. SalB is a major component of the Salvia miltiorrhiza root and has been shown to be an effective treatment for subarachnoid hemorrhages and myocardial infarctions. HeLa cells were cultured in 12-well plates and treated with SalB (100 or 10 ㎍/ml) and 10⁶ PFU/ml of EV71. SalB treatment (100 ㎍/ml) significantly decreased the cleavage of the eukaryotic eIF4G1 protein and reduced the expression of the EV71 capsid protein VP1. In addition, SalB treatment showed a dramatic decrease in viral infection, measured by immunofluorescence staining. The Akt signaling pathway, a key component of cell survival and proliferation, was significantly increased in EV71-infected HeLa cells treated with 100 ㎍/ml SalB. RT-PCR results showed that the mRNA for anti-apoptotic protein Bcl-2 and the cell cycle regulator Cyclin-D1 were significantly increased by SalB treatment. These results indicate that SalB activates Akt/PKB signaling and inhibits apoptosis in infected HeLa cells. Taken together, these results suggest that SalB could be used to develop a new therapeutic drug for EV71-induced HFMD.

• Korean Journal of Childcare and Education
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• v.10 no.4
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• pp.119-132
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• 2014

The purpose of this study is to see how young children's playfulness and ability to creatively problem solve can affect their behavior. young children's playfulness in creases with in creasing creativity and personality traits and behavioral problems decrease with increasing of playfulness. Young children's behavioral problems increase with increasing of creative personality traits. In addition, young children's playfulness and creative personality characteristics affect their behavioral problems. The impact on the behavioral problems with variables for playfulness and creative personality traits has a negative correlation with creative curiosity, a sense of humor and expression of fun. The cognitive and physical spontaneity of the playfulness are correlated positively to young children's behavioral problems.

• Korean journal of food and cookery science
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• v.13 no.5
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• pp.585-591
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• 1997

The proximate composition and physicochemical properties of three cultivars of Korean kidney bean sediments, Pink (PKB), Red (RKD) and White (WKB) were compared. No significant differences in the proximate composition and calorie were noticed among three samples. Sediment granule was oval/round and rough in all samples. The amylograms showed no peak and continuous increase of viscosity during heating. The water-binding capacities of the sediments were 322.4∼355.0%. The swelling power and solubility were 5.93∼6.68% and 3.76∼5.28%, respectively. The percent transmittances of the sediment suspension decreased linearly from 50$^{\circ}$∼75$^{\circ}C$. The gelatinization temperature and gelatinization enthalpy determined by DSC (Differential Scanning Caloriemeter) were much lower than those of starches.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3103-3107
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• 2012

Osteosarcoma, the most common primary mesenchymal malignant tumor, usually has bad prognosis in man, with cancer stem-like cells (CSCs) considered to play a critical role in tumorigenesis and drug-resistance. It is known that phosphatidylinositol 3-kinase (PI3K) is involved in regulation of tumor cell fates, such as proliferation, cell cycling, survival and apoptosis. Whether and how PI3K and inhibitors might cooperate in human osteosarcoma CSCs is still unknown. We therefore evaluated the effects of LY294002, a PI3K inhibitor, on the cell cycle and apoptosis of osteosarcoma CSCs in vitro. LY294002 prevented phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K phosphorylation activity, thereby inducing G0/G1 cell cycle arrest and apoptosis in osteosarcoma CSCs. Further studies also demonstrated that apoptosis induction by LY294002 is accompanied by activation of caspase-9, caspase-3 and PARP, which are involved in the mitochondrial apoptosis pathway. Therefore, our results indicate PI3K inhibitors may represent a potential strategy for managing human osteosarcoma via affecting CSCs.