• Microbiology and Biotechnology Letters
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• v.38 no.1
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• pp.19-23
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• 2010

Recently, marine organisms are emerging as a leading group for identifying and extracting novel bioactive substances. These substances are known to possess a potential regarding not only as a source of pharmaceutical products but also their beneficial effects on humans. Among the substances, antimicrobial peptides (AMPs) specifically have attracted considerable interest for possible use in the development of new antibiotics. AMPs are characterized by relatively short cationic peptides containing the ability to adopt a structure in which cationic or hydrophobic amino acids are spatially scattered. Although a few reports address novel marine organisms-derived AMPs, their antimicrobial mechanism(s) are still remain unknown. In this review, we summarized the peptides previously investigated, such as Pleurocidin, Urechistachykinins, Piscidins and Arenicin-1. These peptides exhibited significant antimicrobial activities against human microbial pathogens without remarkable hemolytic effects against human erythrocytes, and their mode of actions are based on permeabilization of the plasma membrane of the pathogen. Therefore, the study of antimicrobial peptides derived from marine organisms may prove to be useful in the design of future therapeutic antimicrobial drugs.

• International Journal of Oral Biology
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• v.32 no.4
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• pp.153-160
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• 2007

The superficial dorsal horn, particularly substantia gelatinosa (SG) in the spinal cord, receives inputs from small-diameter primary afferents that predominantly convey noxious sensation. Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS are also involved in persistent pain through a spinal mechanism. In the present study, whole cell patch clamp recordings were carried out on SG neurons in spinal cord slice of young rats to investigate the effects of hydrogen peroxide on neuronal excitability and excitatory synaptic transmission. In current clamp condition, tert-buthyl hydroperoxide (t-BuOOH), an ROS donor, depolarized membrane potential of SG neurons and increased the neuronal firing frequencies evoked by depolarizing current pulses. When slices were pretreated with phenyl-N-tert-buthylnitrone (PBN) or ascorbate, ROS scavengers, t-BuOOH did not induce hyperexcitability. In voltage clamp condition, t-BuOOH increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), and monosynaptically evoked excitatory postsynaptic currents (eEPSCs) by electrical stimulation of the ipsilateral dorsal root. These data suggest that ROS generated by peripheral nerve injury can modulate the excitability of the SG neurons via pre- and postsynaptic actions.

• KSBB Journal
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• v.26 no.5
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• pp.433-438
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• 2011

These studies were conducted to investigate the alcohol degradation effects of the extract of herbal composition (DTS20) containing Viscum album L., Lycium chinense L., Inonotus obliquus and Acanthopanax senticosus H., on the alcohol administered mice. To investigate anti-hangover effect, alcohol and alcohol dehydrogensae (ADH) concentration of blood were measured after oral administration of ethanol. The administration of DTS20 (200-500 mg/kg) had beneficial actions toward alcohol degradation in acute alcohol treated mice model. The oral administration of DTS20 showed decreased gastric mucous membrane damage produced in ethanol treated mice. In addition, intraperitoneal administration of DTS20 showed anti-inflammatory effects in inhibition tests of vascular permeability produced by acetic acid. DTS20 also reduced the concentration of nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$ in macrophages that were activated by LPS. These results demonstrate that DTS20 possesses potential to stimulate the alcohol degradation and inhibit the inflammatory effects in mice.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.66-78
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• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.

• Archives of Pharmacal Research
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• v.18 no.2
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• pp.113-117
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• 1995

We re-cloned mouse ${\delt}-Opioid$receptor from NG108-15 cells using RT-PCR, and confirmed it by restriction analysis and by sequencing the beginning and end part of the amplified DNA. When transiently expressed in COS-7 cells, cloned ${\delt}-Opioid$ receptor showed saturable and specific binding to $[^3H]$naloxone with very similar binding parameters to originally reported ones. To make antibodies specific for the ${\delt}-Opioid$ receptor, the carboxy tail of the receptor, which is unique to the ${\delt}-Opioid$ receptor compared with other opioid receptors, was expressed in bacteria as a ufsion proteinwith glutathione S-transferase. Purified fusion protein selective for ${\delt}-Opioid$ receptor when tested by western blotting using membrane proteins prepared from transfected COS-7 cells. Cloned ${\delt}-Opioid$ receptor andl antibodies specific for ${\delt}-Opioid$ receptor are going to be valuable tools for studying pharmacological actions of the ${\delt}-Opioid$ receptor and morphine dependence.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.26 no.1
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• pp.107-124
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• 2000

A bacterial strain No. HB-5, which was capable of producing a pretense in the culture conditions, was isolated from the soil . The pretense was purified from cultural filtrate of Bacillus sp. HB-5 by membrane ultrafiltration and DEAE- cellulose chromatography, gel filtration on Sephadex G-100. The molecular weight was estimated to be 60k4a. The optimal pH and temperature for the activity of the purified pretense pH were 11 and 5$0^{\circ}C$ , respectively. The enzyme was stable within a pH range 8-12 and up to 6$0^{\circ}C$ . The enzyme activity was highly inhibited by PMSF at 1mM. The proteolytic actions of pretense and papain on human epidermis keratins which are major protein impurities on the skin, were compared. The bacterial pretense degraded more effectively than papain. Product containing 2% protease exhibited 21% increase on the skin coloration index. These results suggest that cosmetic product containing pretense produced by Bacillus sp. HB-5 could remove the adherent keratin layer and then make a softer skin.

• Molecules and Cells
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• v.45 no.4
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• pp.169-176
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• 2022

A primary cilium, a hair-like protrusion of the plasma membrane, is a pivotal organelle for sensing external environmental signals and transducing intracellular signaling. An interesting linkage between cilia and obesity has been revealed by studies of the human genetic ciliopathies Bardet-Biedl syndrome and Alström syndrome, in which obesity is a principal manifestation. Mouse models of cell type-specific cilia dysgenesis have subsequently demonstrated that ciliary defects restricted to specific hypothalamic neurons are sufficient to induce obesity and hyperphagia. A potential mechanism underlying hypothalamic neuron cilia-related obesity is impaired ciliary localization of G protein-coupled receptors involved in the regulation of appetite and energy metabolism. A well-studied example of this is melanocortin 4 receptor (MC4R), mutations in which are the most common cause of human monogenic obesity. In the paraventricular hypothalamus neurons, a blockade of ciliary trafficking of MC4R as well as its downstream ciliary signaling leads to hyperphagia and weight gain. Another potential mechanism is reduced leptin signaling in hypothalamic neurons with defective cilia. Leptin receptors traffic to the periciliary area upon leptin stimulation. Moreover, defects in cilia formation hamper leptin signaling and actions in both developing and differentiated hypothalamic neurons. The list of obesity-linked ciliary proteins is expending and this supports a tight association between cilia and obesity. This article provides a brief review on the mechanism of how ciliary defects in hypothalamic neurons facilitate obesity.

• Proceedings of the Korean Nutrition Society Conference
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• 1995.11b
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.71-81
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• 1988

Glutamate and aspartate may evoke an increase in membrane permeability to monovalent cations and $Ca^{++}$. However, it is uncertain whether $Ca^{++}$ influx is mediated by voltage dependent $Ca^{++}$ channels or by excitatory amino acid activated channels. In addition, the influences of excitatory amino acids on $Ca^{++}$ uptake by neuronal tissues as well as the responses of their actions to extracellular $Mg^{++}$ concentration are different. $K^{+}$ induced $Ca^{++}$ uptake by synaptosomes was dependent on extracellular $Mg^{++}$ up to 5 mM and at concentration of 10 mM, $Ca^{++}$ influx was rather reduced. In $Na^{+}$ rich media, glutamate-and aspartate-induced $Ca^{++}$ uptake was increased by $Mg^{++}$ in a dose independent manner. However, the response for NMDA was inhibited by $Mg^{++}$ at concentrations above 2 mM. $K^+$-and glutamate-induced $Ca^{++}$ influx s were inhibited by 2,4-dinitrophenol, chlorprom-azine and verapamil but not by tetraethylammonium chloride. Tetrodotoxin effectively inhibited the action of glutamate but did not affect that of $K^+$. The response for MNDA was inhibited by 2, 4-dinitrophenol and tetrodotoxin, slightly inhibited by verapamil, and not affected by tetraethylammonium chloride. In $Na^{++}$ rich medium, depolarizing action of glutamate, aspartate and MNDA on synaptosomes was not demonstrated, whereas these agents stimulated $Ca^{++}$ uptake and caused $Ca^{++}$ influx induced depolarization at mitochondria. On the other hand, the activities of synaptosomal ATPases were not affected by excitatory amino acids at 5 mM. The results suggest that glutamate or NMDA induced $Ca^{++}$ influx at synaptosomes exhibits different responses for extracellular $Mg^{++}$ Ex citatory amino acids induced $Ca^{++}$ influx at synaptosomes may be associated with increased permeability of membrane for $Na^{++}$ and $Ca^{++}$ except $K^{++}$ and membrane depolarization due to increased ionic permeability.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.625-637
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• 1997

Calcium ions are implicated in a variety of physiological functions, including enzyme activity, membrane excitability, neurotransmitter release, and synaptic transmission, etc. Calcium antagonists have been known to be effective for the treatment of exertional angina and essential hypertension. Selective and nonselective voltage-dependent calcium channel blockers also have inhibitory action on the acute and tonic pain behaviors resulting from thermal stimulation, subcutaneous formalin injection and nerve injury. This study was undertaken to investigate the effects of iontophoretically applied $Ca^{++}$ and its antagonists on the responses of WDR (wide dynamic range) cells to sensory inputs. The responses of WDR cells to graded electrical stimulation of the afferent nerve and also to thermal stimulation of the receptive field were recorded before and after iontophoretical application of $Ca^{++}$, EGTA, $Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA, ${\omega}-conotoxin$ MVIIC and ${\omega}-agatoxin$ IVA. Also studied were the effects of a few calcium antagonists on the C-fiber responses of WDR cells sensitized by subcutaneous injection of mustard oil (10%). Calcium ions and calcium channel antagonists ($Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA & ${\omega}-agatoxin$ IVA) current-dependently suppressed the C-fiber responses of WDR cells without any significant effects on the A-fiber responses. But ${\omega}-conotoxin$ MVIIC did not have any inhibitory actions on the responses of WDR cell to A-fiber, C-fiber and thermal stimulation. Iontophoretically applied EGTA augmented the WDR cell responses to C-fiber and thermal stimulations while spinal application of EGTA for about $20{\sim}30\;min$ strongly inhibited the C-fiber responses. The augmenting and the inhibitory actions of EGTA were blocked by calcium ions. The WDR cell responses to thermal stimulation of the receptive field were reduced by iontophoretical application of $Ca^{++}$, verapamil, ${\omega}-agatoxin$ IVA, and ${\omega}-conotoxin$ GVIA but not by ${\omega}-conotoxin$ MVIIC. The responses of WDR cells to C-fiber stimulation were augmented after subcutaneous injection of mustard oil (10%, 0.15 ml) into the receptive field and these sensitized C-fiber responses were strongly suppressed by iontophoretically applied $Ca^{++}$, verapamil, ${\omega}-conotoxin$ GVIA and ${\omega}-agatoxin$ IVA. These experimental findings suggest that in the rat spinal cord, L-, N-, and P-type, but not Q-type, voltage-sensitive calcium channels are implicated in the calcium antagonist-induced inhibition of the normal and the sensitized responses of WDR cells to C-fiber and thermal stimulation, and that the suppressive effect of calcium and augmenting action of EGTA on WDR cell responses are due to changes in excitability of the cell.