• Biomolecules & Therapeutics
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• v.13 no.4
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• pp.251-255
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• 2005

In the present study, we tried to investigate whether protein kinase C (PKC) activator, phorbol 12-Myristate 13-Acetate (PMA), and PKC inhibitors, $G\"{o}-6976$, Ro-31-8220 and rottlerin significantly affect basal mucin relesed from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3H$-glucosamine for 24 hr and chased for 30 min in the presence of each agent to assess the effects on $^3H$-mucin release. The results were as follows: (1) PMA increased mucin release from cultured HTSE cells, during 30 min of treatment period; (2) However, $G\"{o}-6976$, Ro-31-8220 and rottlerin did not significantly affect mucin release, during 30 min of treatment period. This finding suggests, at least in part, that PKC might playa minor role in the signaling pathways involved in basal - physiological or constitutive - mucin release from airway goblet cells, although further studies are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1085-1091
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• 2014

Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.

• Journal of Microbiology and Biotechnology
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• v.12 no.6
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• pp.895-900
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• 2002

A soil microorganism producing ${\alpha}$- and ${\beta}$-glucosidase inhibitors was identified as Bacillus lentimorbus, based on the fatty acid and morphological analyses, along with biochemical and physiological tests. The ${\alpha}$-glucosidase inhibitor was highly produced by this strain in a culture medium containing $0.25\%$ of sodium glutamate and $0.5\%$ of glucose, pH 8.0 at $30^{\circ}C$ for 2 days. The ${\alpha}$-glucosidase inhibitor from culture filtrate of his strain was identified as water soluble, organic solvent nonextractable, and heat stable. In addition to ${\alpha}$-glucosidase inhibitor, this strain also produced ${\beta}$-glucosidase inhibitor in he same culture medium and this inhibitor showed an antifugal activity against Botrytis cinerea. While the production of ${\alpha}$- glucosidase inhibitor was decreased by a glucose concentration higher than $1\%$, the production of ${\beta}$-glucosidase inhibitor was lot Influenced by a glucose concentration higher than $20\%$. The ${\alpha}$-glucosidase inhibitor from culture filtrate of this strain was separated from the ${\beta}$-glucosidase inhibitor through Sephadex G-100 column chromatography.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.365-368
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• 2008

Calcium entry through $Ca_v3.2Ca^{2+}$ channels plays essential roles for various physiological events including thalamic oscillation, muscle contraction, hormone secretion, and sperm acrosomal reaction. In this study, we examined how protein tyrosine phosphatases or protein tyrosine kinases affect $Ca_v3.2Ca^{2+}$ channels reconstituted in Xenopus oocytes. We found that $Ca_v3.2$ channel activity was reduced by 25% in response to phenylarsine oxide (tyrosine phosphatase inhibitor), whereas it was augmented by 19% in response to Tyr A47 or herbimycin A (tyrosine kinase inhibitors). However, other biophysical properties of $Ca_v3.2$ currents were not significantly changed by the drugs. These results imply that $Ca_v3.2$ channel activity is capable of being increased by activation of tyrosine phosphatases, but is decreased by activation of tyrosine kinases.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.129-135
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• 2020

SHP2 is an unusual protein phosphatase that functions as an activator for several signaling pathways, including the RAS pathway, while most other phosphatases suppress their downstream signaling cascades. The physiological and pathophysiological roles of SHP2 have been extensively studied in the field of cancer research. Mutations in the PTPN11 gene which encodes SHP2 are also highly associated with developmental disorders, such as Noonan syndrome (NS), and cognitive deficits including learning disabilities are common among NS patients. However, the molecular and cellular mechanism by which SHP2 is involved in cognitive functions is not well understood. Recent studies using SHP2 mutant mice or pharmacological inhibitors have shown that SHP2 plays critical role in learning and memory and synaptic plasticity. Here, we review the recent studies demonstrating that SHP2 is involved in synaptic plasticity, and learning and memory, by the regulation of the expression and/or function of glutamate receptors. We suggest that each cell type may have distinct paths connecting the dots between SHP2 and glutamate receptors, and these paths may also change with aging.

• The Korean Journal of Physiology
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• v.21 no.2
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• pp.283-289
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• 1987

Uric acid transport across the basolateral membrane of renal proximal tubules was studied in rabbit kidney cortical slices. Uric acid uptake was greater under $O_2$ atmosphere compared to under $N_2$ atmosphere, and was increased with $Na^{2+}$ concentration in incubation medium. Uric acid inhibited PAH uptake but not TEA uptake and did trans-stimulated PAH efflux. PAH also inhibited uric acid uptake. Uric acid uptake was inhibited by harmaline, ouabin, SITS, DIDS and pyrazinoic acid. The inhibition of PAH uptake by these inhibitors also was reasonably comparable to that of uric acid uptake. These results suggest that uric acid was transported across the basolateral membrane of renal tubule by a carrier-mediated process which was by a common transport system with PAH in rabbit.

• BMB Reports
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• v.41 no.4
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• pp.278-286
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• 2008

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been approved for use to treat patients with colorectal, lung, renal and liver cancers. These drugs have opened a novel field of cancer therapy, i.e. anti-angiogenesis therapy. However, as yet they cannot completely cure patients, and cancer cells could become resistant to these drugs. Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy.

• BMB Reports
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• v.51 no.5
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.109-109
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• 2003

Taurine is present in a variety of tissue and exhibits many important physiological functions in many tissues. Although it is known that many tissues mediate taurine transport, its functions of taurine transport in bone have not been identified yet. In the present study, we investigated the expression of taurine transporter (TauT) and taurine uptake using mouse stromal ST2 cells and osteoblast-like MC3T3-El cells, which is bone related cells. Detection of TauT mRNA expression in these cells were performed by reverse transcription polymerase chain reaction (RT-PCR). The activity of TauT was assessed by measuring the uptake of ［$^3$H］taurine in the presence or absence of inhibitors. TauT mRNA was detected in these cells. ［$^3$H］Taurine uptake was dependent upon the presence of extracellular sodium, chloride and calcium ions, and inhibited by cold-taurine and ${\beta}$-alanine. These results suggest that taurine has biological functions in bone and some effect on the bone cells.

• 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.