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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules & Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 12, Issue 4 - Dec 2004
Volume 12, Issue 3 - Sep 2004
Volume 12, Issue 2 - Jun 2004
Volume 12, Issue 1 - Mar 2004
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Secretory Differentiation of Hamster Tracheal Epithelial Cells Increases Activation of Matrix Metalloproteinase-2
Shin, Chan-Young ; Lee, Woo-Jong ; Park, Kyu-Hwan ; Ryu, Jae-Ryun ; Ko, Kwang-Ho ;
Biomolecules & Therapeutics, volume 12, issue 1, 2004, Pages 1~8
In chronic airway inflammatory diseases such as asthma and chronic bronchitis, it has been suggested that matrix metalloproteinases secreted from infiltrating neutrophil contribute the pathogenesis of the disease and have been a focus of intense investigation. We report here that hamster tracheal surface epithelial goblet cells (HTSE cells) produce matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2). Matrix metalloproteinase activities were investigated using [
]collagen-digestion assay and gelatin zymography. The subtype of matrix metalloproteinases expressed from HTSE cells was MMP-2 (gelatinase A), which was determined by Western blot with various subtype selective anti-matrix metalloproteinase antibodies. The MMP-2 and TIMP-2 cDNAs from HTSE cells were partially cloned by RT-PCR and they reveal more than 90% of sequence homology with those from human, rat and mouse. The collagenolytic activity was increased with the secretory differentiation of the HTSE cell and it was found that zymogen activation was responsible for the increased MMP-2 activity in HTSE cells. The results from the present study suggest that the metaplastic secretory differentiation of airway goblet cells may affect chronic airway inflammatory process by augmenting the zymogen activation of MMP-2.
Differential Effect of Harmalol and Deprenyl on Dopamine-Induced Mitochondrial Membrane Permeability Change in PC12 Cells
Lee, Chung-Soo ;
Biomolecules & Therapeutics, volume 12, issue 1, 2004, Pages 9~18
Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of
-carbolines (harmaline and harmalol) and deprenyl on the dopamine-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. Cell death due to 250
M dopamine was inhibited by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, ascorbate, superoxide dismutase, catalase and carboxy-PTIO).
-Carbolines prevented the dopamine-induced cell death in PCl2 cells, while deprenyl did not inhibit cell death.
-Carbolines decreased the condensation and fragmentation of nuclei caused by dopamine in PC12 cells.
-Carbolines inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, formation of reactive oxygen species and depletion of GSH caused by dopamine in PC12 cells, whereas deprenyl did not decrease dopamine-induced mitochondrial damage.
-Carbolines, deprenyl and antioxidants depressed the formation of nitric oxide and melanin in dopamine-treated PC12 cells. The results suggest that cell death due to dopamine PC12 cells is mediated by caspase-8, -9 and -3. Unlike deprenyl,
-carbolines may attenuate the dopamineinduced cell death in PC12 cells by suppressing change in the mitochondrial membrane permeability through inhibition of the toxic action of reactive oxygen and nitrogen species.
Antihypertensive Effect of Amlodipine Adipate, a Novel Salt of Amlodipine, in Hypertensive Rat Models
Lee, Byung-Ho ; Seo, Ho-Won ; Chae, Myeong-Yun ; Yeon, Kyu-Jeong ;
Biomolecules & Therapeutics, volume 12, issue 1, 2004, Pages 19~24
The vascular relaxant effect of amlodipine adipate, a new salt of amlodipine, was evaluate in isolated rat aorta, and compared with that of amlodipine besylate. Furthermore, antihypertensive effects were measured in hypertensive rat models, such as spontaneously hypertensive rats (SHR) and rena1 hypertensive rats (RHR). Amlodipine adipate concentration-dependently inhibited
-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5 h;
: 3.76 nM), having a pattern and a potency similar to those of amlodipine besylate (
: 4.01 nM). In SHR and RHR, orally administered amlodipine adipate produced a dosedependent and long-lasting (>10-24 h) antihypertensive effect (
: 2.48 and 1.57 mg/kg, respectively), with a pattern and a potency similar to those of amlodipine besylate (
: 2.50 and 1.99 mg/kg in SHR and RHR, respectively). These results suggest that amlodipine adipate is a potent and long-lasting antihypertensive agent and that its antihypertensive effect is not significantly different to that of amlodipine besylate.
Glucose Deprivation and Immunostimulation Induced Death in Rat Primary Astrocytes is Mediated by Their Synergistic Effect on the Decrease in Cellular ATP Level
Choi, Ji-Woong ; Yoo, Byoung-Kwon ; Yoon, Seo-Young ; Jeon, Mi-Jin ; Ko, Kwang-Ho ;
Biomolecules & Therapeutics, volume 12, issue 1, 2004, Pages 25~33
In this study we investigated whether ATP loss was involved in the potentiated death of immunostimulated rat primary astrocytes in glucose-deprived condition. Rat primary astrocytes immunostimulated with LPS plus IFN-
for 48 h underwent death upon glucose deprivation, which dependent on the production of peroxynitrite. Intracellular ATP level synergistically decreased by glucose deprivation in immunostimulated astrocytes but not in control cells, and the loss of ATP occurred well ahead of the LDH release. The synergistic cell death and ATP loss by immunostimulation and glucose deprivation were inhibited by iNOS inhibitor (L-NAME and L-NNA) or peroxynitrite decomposition catalyst (also a superoxide anion scavenger), Mn(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (MnTMPyP). Exogenous addition of peroxynitrite generator, SIN-l timedependently induced ATP loss and cell death in the glucose-deprived astrocytes. Depletion of intracellular glutathione (GSH) and dis겨ption of mitochondrial transmembrane potential (MTP) were also observed under same conditions. Supply cellular ATP by the addition of exogenous adenosine or ATP during glucose deprivation inhibited ATP depletion, GSH depletion, MTP disruption and cell death in SIN-l treated or immunostimulated astrocytes. This study showed that perturbation in the regulation of intracellular ATP level in immunostimulated astrocytes might make them more vulnerable to energy challenging stimuli.
Anti-stress Effect of Scutellatia baicalensis in SD Rats and ICR Mice
Ryu, Jong-Hoon ; Tan-Lee, Blendyl Saguan ; Jung, Ji-Woong ; Ahn, Nam-Yoon ; Lee, Seung-Joo ; Yu, Gu-Young ; Han, Shin-Ha ; Lee, Jeong-Hoon ; Lee, Geum-Seon ; Cheong, Jae-Hoon ;
Biomolecules & Therapeutics, volume 12, issue 1, 2004, Pages 34~42
The aim of this study is to investigate anti-stress effect of Scutellaria baicalensis(SB). The experiments were performed with the use of young (9 weeks of age) male rats of SD strain and the male ICR mice (20-25 g) at the time of first treatment with SB. Animals of the normal group were not exposed to any stress and the control group were exposed to stress. The rats of the Ginseng, Diazepam(BZ) and SB supplementary group were orally administered once a day 100 mg of red ginseng extract, 5 mg of BZ or 100 mg of SB extract/kg body weight and they were exposed to stress. The mice of the Ginseng, BZ and SB supplementary group were given water containing 200 mg of red ginseng extract, 10 mg of BZ or SB extract/100 ml potable water and exposed to stress. Animals were given supplements for 7 days without stress, and then were given supplement for 5 days with restraining and electroshock stress. We recorded stress related behavioral changes of the experimental animals by stressing them using the Etho-vision system and measured levels of blood corticosterone and IL-2. SB supplementation partially blocked the stress effect on locomotion in the rats and mice, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, grooming, smelling, and rearing behavior in the rats and smelling, grooming, tailing, and rearing in the mice. in elevated plus maze test, the staying time of the stressed rats and mice in the open area decreased while it increased in the closed area. But these changes also partially were blocked by SB-supplementation. SB-supplementation decreased levels of the blood corticosterone which was increased by stress in the rats but did not significantly increase levels of blood interleukin 2 which was decreased by stress in mice.
Acute Toxicity of CKD-602, a New Anticancer Agent, in Rats
Kim, Jong-Choon ; Shin, Dong-Ho ; Kim, Sung-Ho ; Kim, Joon-Kyun ; Cha, Shin-Woo ; Han, Jung-Hee ; Suh, Jeong-Eun ; Chung, Moon-Koo ;
Biomolecules & Therapeutics, volume 12, issue 1, 2004, Pages 43~48
The present study was carried out to investigate the potential acute toxicity of CKD-602 by a single intravenous dose in Sprague-Dawley rats. Ten males females were used in each test groups: a vehicle control, 34.7, 4l.7, 50.0, 60.0 and 72.0 mg/kg groups, and were given different single intravenous doses of CKD-602 to the test animals. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of l4-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. One, 1, 2, 8 and 9 cases of deaths occurred in the male dose groups of 34.7, 41.7, 50.0, 60.0 and 72.0 mg/kg, respectively, and 1, 5 and 9 cases in the female dose groups 50.0, 60.0 and 72.0 mg/kg, respectively. An increase in the incidence of clinical signs such as alopecia, skin pallor skin ulcerations, emaciation and change of fecal material was found in the both sexes of all treatment groups. A decrease or Suppression in the body weight was also observed in a dose-dependent manner. In autopsy, male and/or female rats of the treatment groups showed treatment-related gross findings such as splenomegaly, atrophy of the testis, epididymis, seminal vesicles, ovary, uterus and thymus which were dose-dependent in incidence and severity. Based on these results, it was concluded that a single intravenous injection of CKD-602 to rats caused significant toxicities in gastrointestinal, hematopoietic, and reproductive systems. The
value was 53.8 (95% confidence limit: 48.5~60.6) mg/kg for males and 60.l (95% confidence limit: 55.3~65.8) mg/kg for females. The
value was 39.9 (95% confidence limit: 3l.7~44.8) mg/kg for males and 50.3 (95% confidence limit: 40.6~54.8) mg/kg for females.
Toxicity Study of CKD-602, a Camptothecin Anticancer Agent: 5-Day Repeated Intravenous Administration in Rats
Han, Jung-Hee ; Cha, Shin-Woo ; Kim, Choong-Yong ; Lee, Gab-Soo ; Suh, Jeong-Eun ; Kim, Joon-Kyum ; Kim, Jong-Choon ; Kang, Boo-Hyon ;
Biomolecules & Therapeutics, volume 12, issue 1, 2004, Pages 49~54
The present study was conducted to investigate the potential subacute toxicity of CKD-602 by a 5-day repeated intravenous administration in Sprague-Dawley rats. CKD-602 was administered intravenously to male rats at dose levels of 0, 0.08, 0.2, and 0.5 mg/kg for 5 days. Studies included general observation, body weight changes, ophthalmoscopic examination, hematology, se겨m biochemistry, gross findings at necropsy and organ weight measurement. There were no deaths in any treatment group and treatment related clinical sign was depilation in the 0.5 mg/kg groups. The decrease or suppression of body weight was also observed dose-dependently in all treatment groups. Decreased leukocyte in all treatment groups, decreased platelet in the above 0.2 mg/kg groups and increase in the serum levels of total cholesterol in the 0.5 mg/kg group were considered as a treatment related toxic effects. Decreased weight of thymus in all treatment groups anti decreased weight of spleen in the above 0.2 mg/kg group were observed. The intravenous administration of CKD-602 caused depilation and decreased weight and had toxic effect on the leukocyte, platelet, spleen and thymus. In the condition of this study, the target organs were spleen and thymus and the toxic effect level was determined to be 0.2 mg/kg, but no-observed-adverse-effect level (NOAEL) was considered to be lower than 0.08 mg/kg.