• Toxicological Research
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• v.17
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• pp.117-125
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• 2001

Envenoming by Russells viper causes a broad spectrum of renal impairment. Renal failure is an important complication in patients bitten by Russells viper. Experimental work in animals and in vitro has elucidated pathophysiological mechanisms that contribute to life threatening complications and have suggested possibilities for therapeutic intervention. The evidence in experimental animals regarding mechanisms of venom action in relation to changes in either extrarenal or intrarenal factors is presented. The cardiovascular system and renal hemodynamics are affected by venom. Reductions of renal function including renal hemodynamics are associated directly with changes in general circulation during envenomation. Possible endogenous mechanisms for releasing the hormone inducing renal vasoconstriction after envenomation are evident. Hormonal factor such as the catecholamine, prostaglandin and renin angiotensin systems induce these changes. Direct nephrotoxicity of venom action is studied in the isolated per-fused kidney. Characteristic polarization of the cell membrane, changes of mitochondrial activity and Na-K ATPase in renal tubular cells are observed. Changes in renal function and the cardiovascular system are observed of ter envenomation and are reversed by the administration of Russells viper antivenom (purified equine immunoglobulin, $Fab_2$ fragment). The neutralizing effects are more efficient when the intravenous injection of antivenom is given within 30 min after the envenomation.

• Biomedical Science Letters
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• v.27 no.3
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• pp.170-176
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• 2021

Thapsigargin (TG), a sarco/endoplasmic reticulum (ER) Ca²⁺-ATPase (SERCA) inhibitor, has been widely used as an agonist for platelet aggregation for decades. In this study, we investigated the effect of TG on the release of lactate dehydrogenase (LDH) for platelets and elucidated its mechanism. Platelet LDH release and platelet aggregation were increased by TG treatment; 1,000 nM of TG induced the complete lysis of platelets. Other agonists such as collagen (2.5 ㎍/mL), thrombin (0.1 U/mL), and ADP (10 mM) did not induce significant platelet LDH release despite platelet aggregation. Finally, we investigated the effects of pharmacological inhibitors on TG-induced platelet aggregation and LDH release. SP600125, a JNK inhibitor, and LY294002, a PI-3K inhibitor, inhibited TG-induced platelet LDH release but not platelet aggregation. Forskolin, an adenylyl cyclase activator, also inhibited LDH release without affecting platelet aggregation by TG. These results suggest that the TG-induced platelet aggregation was accompanied by LDH release but regulated by a different signaling pathway.

• Applied Microscopy
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• v.19 no.2
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• pp.119-137
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• 1989

It has been shown in this and earlier investigation that the turtle bladder mucosa has three main cell types on their mucosal surface. They are the granular cells, ${\alpha}$ CA cells, and ${\beta}$ CA cells. The three major transport mechanisms that occurs in the turtle bladder are sodium reabsorption, proton secretion, and bicarbonate secretion. In the present work the trans-port mechanisms by bladder epithelial cells of freshwater turtle, Pseudemys scripta, are summarized as follows. 1. The granular cells play an important role in sodium transport, while the ${\alpha}$ and ${\beta}$ CA cells do not appear to play a determining role in sodium transport. 2. It appears that the active sodium transport in the granular cells occurs in two-step process, implying that first, sodium diffuses into the cells, followed by an energy-dependent efflux step, which is catalyzed by the ouabain-sensitive Na-K ATPase. 3. The ${\alpha}$ type of CA cells are responsible for the proton secretion using the proton pump on the apical plasma membrane, while the ${\beta}$ type of CA cells are believed to be responsible for bicarbonate secretion. 4. When looked at under freeze-fracture electron microscopy, the apical plasma membrane of ${\alpha}$ cells have a characteristic population of rod-shaped intramembranous particles which are believed to be components of the proton pumps. Conversely, ${\beta}$ type of CA cells show rod-shaped particles in their basolateral plasma membranes, which is consistent with the proton absorptive, bicarbonate secretory mechanism. 5. In the turtle bladder, the ${\alpha}$ and ${\beta}$ type of cells are believed to be both responsible for proton transport, but in opposite directions.

• Korean Journal of Veterinary Research
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• v.46 no.4
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• pp.323-326
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• 2006

Suaeda (S.) asparagoides $M_{IQ}$, one of the halophyte groups, has been used as a folk remedy for digestive disturbances in Korea. However, its pharmacological activity on gastrointestinal motility has not been reported yet. In this study, the effects of this halophyte extracts with various solvent fractions (ethanol, hexane, chloroform, ethyl acetate, butanol, and water) on mice ileal spontaneous motility was examined. All solvent fractions at the concentration of $100{\mu}g/ml$ showed inhibitory actions on spontaneous motility of ileum with the potency order of water > 70% ethanol > hexane ${\gg}$ chloroform ${\geq}$ butanol ${\geq}$ ethyl acetate, respectively. In addition, the water fraction of extracts from S. asparagoides $M_{IQ}$ (WFSA) dose-dependently ($1-100{\mu}g/ml$) inhibited the amplitude of spontaneous phasic contraction and area under the contractile curve (AUC). The inhibitory effect of water fraction at the concentration of $10{\mu}g/ml$ was not affected by tetrodotoxin (TTX), $Na^+$ channel blocker ($1{\mu}M$), and $N^w$-nitro-L-arginine Methyl Ester (L-NAME), nitric oxide synthase inhibitor ($100{\mu}M$). However, cyclopiazonic acid (CPA, $10{\mu}M$), inhibitor of sarcoplasmic reticulum $Ca^{2+}$-ATPase, almost blocked the inhibitory effects of WFSA ($10{\mu}g/ml$) on the spontaneous phasic contraction of mouse ileum. But, CPA did not inhibit the lowering basal tone effects of WFSA. The result of this study showed that various extracts of S. asparagoides $M_{IQ}$ induce inhibitory effects on spontaneous contraction of mice ileal segments. More over, the polar solvent fractions were shown to be more potent than non-polar solvent fractions. The effects of S. asparagoides $M_{IQ}$ extracts are not mediated by nerve or nitric oxide. The inhibitory effects of WFSA at least partially mediated by sarcoplasmic reticulum $Ca^{2+}$-ATPase. However, further study is required to determine the exact pharmacological mechanisms of this halophyte on its gastrointestinal motility inhibitory effects.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.18 no.5
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• pp.455-463
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• 1985

Thermal-denaturation of myofibrillar protein of dorsal skeletal muscle from file fish was investigated by measuring denaturation constant($K_D$) and thermodynamic parameters at various temperatures. The protective effects of sucrose, sorbitol and amino acids when added individually or combined were also discussed. The denaturation rate as reflected in inactivation of myofibrillar protein Ca-ATPase was followed the first order reaction. The $K_D$ values at $25^{\circ}C,\;30^{\circ}C,\;and\;35^{\circ}C$ were $19.52{\times}10^{-5},\;112.25{\times}10^{-5},\;and\;247.20{\times}10^{-5}$, respectively. The activation energy of the reaction at $30^{\circ}C$ was 43 kcal/mole. The protective effects of sucrose, sorbitol, glycine, alanine and Na-glutamate were increased with the concentration but the effects of sorbitol and Na-glutamate decreased beyond 1.0 mole. Basic amino acids such as arginine and lysine did not revealed any protective effect on the thermal denaturation. In case of mixed addition, the effects of Na-glutamate to glycine, sorbitol to glycine, and sorbitol to sucrose or sorbitol to Na-glutamate were enhanced 1.2 to 7.0 times as much as that of control (ratio of mixing; 1:1, range of concentration; 0.5 to 1.25 mole). Under the frozen condition at $-20^{\circ}C$, two mixtures such as Na-glutamate to glycine and sorbitol to sucrose apparently revealed the protective effects.

• Journal of environmental and Sanitary engineering
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• v.11 no.2
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• pp.21-26
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• 1996

In our previous studies, we reported that lead intoxicated nerve cell by inhibition of the Na$^{+}$-K$^{+}$ ATPase activity and reduction of myo-inositol in nerve cell. As the second series of experiments, in order to understand toxic mechanism of lead for nerve cell, the characteristics of myo-inositol transport system and the effect of lead on its system have been studied in the sciatic nerves of control and lead-treated rats. A lead intoxicated animal model was induced by feeding diet containing lead to Sprague-Dawley rat for two weeks. Four weeks aged Sprague-Dawley rats were divided into three group : normal control group, 10ppm-lead treated group, 100ppm-lead treated group. All rats were sacrified at the end of two weeks. The rate o myo-inositol transport by sciatic nerve isolated from lead-treated rat was significantly decreased compared with that of control rat. This deficit results from that myo-inositol transport system which is carrier mediated and sodium-potassium dependent was inhibited by the lead treatment (both 10ppm and 100ppm) due to increase of the Km value without affecting Vmax value for myo-inositol carrier. These observations suggest that the toxic mechanism of lead on nerve myo-inositol transport system might be a change of affinity without change of maximum transport velocity for carrier.

• Proceedings of the Korean Society for Food Science of Animal Resources Conference
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• 2005.10a
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• pp.334-338
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• 2005

식육의 소비형태가 변화함에 따라 생체 기능성물질의 탐색과 이용에 관한 연구가 활성화 되어지고 있다. 식품에 소량 존재하며 지방세포분화를 촉진하는 물질로 밝혀진 conjugated linoleic acid (CLA)중 9c-11c(9c)가 3원 교잡종 암퇘지(Yorkshire ${\times}$ Landrace ${\times}$ Duroc)의 어떤 유전자에 영향을 줌으로써 지방세포의 분화를 촉진하는지 DNA chip을 이용하여 분석하였다. 분석도구로는 Genepix 6.0과 Vector Xpression 3.0을 사용하였다. 분석결과 $Na^+,\;K^+$-ATPase, ciliary neurotrophic factor, complement cytolysis inhibitor, prolactin receptor, type II collagen alpha1 등 과 같은 분화 관련 유전자가 나타났다. 이 연구는 나아가 DNA chip을 이용해서 지방세포 분화억제에 관여하는 유전자를 찾아내고, 이 유전자들은 지방세포 분화 조절과 비만관련 연구에 활용될 것이다.

• The Korean Journal of Zoology
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• v.38 no.1
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• pp.96-105
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• 1995

본 연구는 옴개구리(Rana rugosa)의 생식주기를 파악하고 이들 난자들의 체외 성숙조건을 구하기 위하여 수행하였다 개구리들의 gonadosomatic index(G51)는 4월에서 8월사이에는 비교적 낮았고 9월에서 이듬해 3월까지는 높았다 여포들의 성장은 주로 6월에서 9월 사이에 이루어지는데 난소내에서도 여포들의 성장 속도는 일부 다른 것으로 나타났다. 야외 관찰에서 이 개구리들은 서식지의 온도에 따라 4월에서 7월 사이에 산란을 한다는 것과 10월에서 이듬해 3월까지 동면을 한다는 것을 말았다. 산란기에 취한 여포 난자들은 생체외 배양에서 progesterone에 성숙반응(germinal vesicle breakdown(GVBD))을 일으키지 않았다. 그러나 protein klnase C(PKC)의 촉진제인 12-O-tetradecanoylphorbol 13-acetate(TPA) 혹은 Na+/K+ ATPase의 저해제인 ouabain을 progesterone과 동시에 처리했을 때에는 성숙반응을 일으켰다(각각 86%와 80%). TPA 로 핵붕괴를 일으킨 난자의 세포질을 미성숙 난자에 주입하면 미성숙 난자의 핵붕괴를 유도하였으며 성숙된 다른 종의 난자들의 세포질도 이와 같은 효과를 나타내었다. TPA의 성숙유도 효과는 5분의 노출 기간으로도 충분하였으며 PKC의 저해제인 H-7을 처리하면 그 효과가 없어졌다 이러한 결과들은 옴개구리의 난자는 호르몬에 성숙반응을 일으킨지 않으나 PKC 활성화 이후 단계는 정상이라는 것을 의미한다.

• The Korean Journal of Physiology
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• v.20 no.2
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• pp.225-235
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• 1986

Effects of anions on p-Aminohippurate (PAH) transport across the basolateral membrane (BLM) were studied. Basolateral membrane vesicles were isolated from rabbit renal cortex by using a self-orienting Percoll-gradient centrifugation and $Mg^{2+}-precipitation$. The characteristics of the membrane vesicles was examined by marker enzyme activity, membrane orientation and transport studies. The Na-K-ATPase activity in the fraction containing BLM vesicles was enriched 9·fold, and the alkaline phosphatase activity in the fraction containing BBM vesicles was increased 9-fold, compared with those of the homogenate. The transport properties of the two membrane preparations were studied by a rapid filtration technique. The uptake of PAH by BLM was sensitive to changes in medium osmolarity and inhibited by probenecid. When the uptake of $50{\mu}M$ PAH in voltage-clamped BLM vesicles was determined in the presence of various anions in the incubation medium, cis inhibitions by $SO_4\;and\;SSO_3$ were observed in the presence of sodium gradient (out>in). Sodium-dependent PAH uptake was inhibited competitively by external $SO_4$ PAH uptake in BLM vesicles loaded with 20 mM acetate and $SO_4\;or\;200\;{\mu}M$ PAH was significantly stimulated as compared with unloaded vesicles. The extent of trans-stmulation of PAH uptake by $SO_4$. was increased with the inside concentration of $SO_4$. This trans-stimulatory effect by $SO_4$, was observed to be additive in the presence of Na gradient and completely inhibited by 2 mM probenecid and 1 mM SITS. These results demonstrate that PAH/anion exchange is present in BLM of renal cortex and in this exchange mechanism inorganic as well as organic anions are involved as substrates.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.233-239
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• 2017

Intracellular calcium ($Ca^{2+}$) oscillation is an initial event in digestive enzyme secretion of pancreatic acinar cells. Reactive oxygen species are known to be associated with a variety of oxidative stress-induced cellular disorders including pancreatitis. In this study, we investigated the effect of hydrogen peroxide ($H_2O_2$) on intracellular $Ca^{2+}$ accumulation in mouse pancreatic acinar cells. Perfusion of $H_2O_2$ at $300{\mu}M$ resulted in additional elevation of intracellular $Ca^{2+}$ levels and termination of oscillatory $Ca^{2+}$ signals induced by carbamylcholine (CCh) in the presence of normal extracellular $Ca^{2+}$. Antioxidants, catalase or DTT, completely prevented $H_2O_2$-induced additional $Ca^{2+}$ increase and termination of $Ca^{2+}$ oscillation. In $Ca^{2+}$-free medium, $H_2O_2$ still enhanced CCh-induced intracellular $Ca^{2+}$ levels and thapsigargin (TG) mimicked $H_2O_2$-induced cytosolic $Ca^{2+}$ increase. Furthermore, $H_2O_2$-induced elevation of intracellular $Ca^{2+}$ levels was abolished under sarco/endoplasmic reticulum $Ca^{2+}$ ATPase-inactivated condition by TG pretreatment with CCh. $H_2O_2$ at $300{\mu}M$ failed to affect store-operated $Ca^{2+}$ entry or $Ca^{2+}$ extrusion through plasma membrane. Additionally, ruthenium red, a mitochondrial $Ca^{2+}$ uniporter blocker, failed to attenuate $H_2O_2$-induced intracellular $Ca^{2+}$ elevation. These results provide evidence that excessive generation of $H_2O_2$ in pathological conditions could accumulate intracellular $Ca^{2+}$ by attenuating refilling of internal $Ca^{2+}$ stores rather than by inhibiting $Ca^{2+}$ extrusion to extracellular fluid or enhancing $Ca^{2+}$ mobilization from extracellular medium in mouse pancreatic acinar cells.