• Journal of Microbiology and Biotechnology
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• v.14 no.2
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• pp.379-384
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• 2004

Fibroblast growth factor-2 (FGF-2) is known to modulate numerous cellular functions in various cell types, including cell proliferation, differentiation, survival, adhesion, migration, and motility, and also in processes such as wound healing, angiogenesis, and vasculogenesis. FGF-2 regulates the expression of several molecules thought to mediate critical steps during angiogenesis. This study examines the mechanisms underlying FGF-2-induced cell migration, using human umbilical vein endothelial cells (HUVECs). FGF-2 induced the nondirectional and directional migration of endothelial cells, which are inhibited by MMPs and plasmin inhibitors, and induced the secretion of matrix metalloproteinase-3 (MMP3) and MMP-9, but not MMP-l and MMP-2. FGF-2 also induced the secretion of the tissue inhibitor of metalloproteinase-l (TIMP-I), but not of TIMP- 2. Also, the pan-PKC inhibitor inhibited FGF-2-induced MMP-9 secretion. It is, therefore, suggested that FGF-2 induces the migration of cultured endothelial cells by means of increased MMPs and plasmin secretion. Furthermore, FGF-2 may increase MMP-9 secretion by activating the PKC pathway.

• Archives of Pharmacal Research
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• v.28 no.11
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• pp.1257-1262
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• 2005

MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.

• The Journal of Natural Sciences
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• v.10 no.1
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• pp.33-37
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• 1998

Cytokinin is one of major growth regulators in plants. In this study, the gene isopentenyl transferase (jpt) which encodes a key enzyme involved in the biosynthesis of the growth regulator cytokinin isolated from Agrobacterium tumefaciens was introduced ito tobacco plant via Agrobacterium-mediated transformation. The jpt gene was modulated using the proteinase inhibitor II (PI-IIK) promotor. In general, this promoterlipt gene fusion resulted in overproduction of cytokinins throughout the transgenic plants. The overproduction of cytokinin caused dramatic changes in morphology of the plant, including stem thickness and reduced root development. The studies reported in this paper were initiated to examine the consequences of overproduction of cytokinin in plant.

• Journal of Plant Biology
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• v.30 no.2
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• pp.95-108
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• 1987

Effects of allopurinol (2mM), a specific inhibitor of xanthine oxidase, on the growth and metabolism of llantoin in dark grown Chinese cabbage (Brassica campestris L.) seedlings were investigated. Allopurinol treatment maintained the fresh and dry weights of cotyledons at higher levels, but inhibited the elongation of hypocotyls and roots of the seedlings. Total nitrogen content in the cotyledons decreased at slower rate by allopurinol. Accordingly, the levels of total nitrogen contents in the hypocotyls and roots, were depressed by the inhibitor. In the cotyledons, allopurinol began to elevate RNA levels after day 3, which it did not affect DNA level throughout the experiment. Activities of xanthine oxidase (XO:EC 1.2.3.2), uricase (UO:EC 1.7.3.3) and allantoinase (AL:EC 3.5.2.5) in the cotyledons were examined. The activity of XO was not detected, but the accumulation of xanthine by allopurinol treatment presented an indirect evidence of the existence of XO in the organ. Allopurinol kept UO activity high up to day 2 after sowing and depressed AL activity throughout the experiment. By allopurinol treatment, allantoin content was kept high over the control both in cotyledons and roots, but it was kept low in hypocotyls. The level of allantoic acid in the 3 organs were shown to be depressed by allopurinol. These results suggest that allantoin and allantoic acid produced by the degradation of stored and newly synthesized RNA are transported from the storage tissue to hypocotyls and roots as important nitrogen sources for the development of Chinese cabbage seedlings.

• Journal of Microbiology and Biotechnology
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• v.15 no.4
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• pp.909-912
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• 2005

In the course of screening for selective growth inhibitors against the mycelial form of Candida albicans, we isolated a Streptomyces sp. A6792 from soils. The inhibitor was isolated from the above bacterium and identified through several spectral analyses with UV and mass spectrophotometries, and various NMR. The compound was determined to be a macrocyclic dilactone antibiotic, IKD-8344 (molecular weight: 844, molecular formula: $C_{48}H_{76}O_{12}$). The compound selectively inhibited the growth of mycelial form of C. albicans with an MIC of 6.25 ${\mu}g/ml$. It also exhibited strong inhibitory effect preferentially on the mycelial form of various Candida spp. including C. krusei, C. tropicalis, and C. lusitaniae, with MICs ranging from 1.56 to 25 ${\mu}g$/ml. Furthermore, the compound showed no significant toxicity against SPF ICR mice up to 60 mg/kg. These results suggest that IKD-8344 is a useful lead compound for the development of novel antifungal agents, based on the preferential growth inhibition against Candida spp.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.1-13
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• 2007

We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.

• Korean Journal of Plant Tissue Culture
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• v.27 no.2
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• pp.133-136
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• 2000

To evaluate the biological effects of dykellic acid, a novel apoptosis inhibitor, isolated from microorganism on the plant cells, the cell growth, protein contents, and superoxide dismutase (SOD) activity were investigated in suspension cultures of tobacco photomixotrophic cultured (PM) cells on 12 days after different concentration of chemical treatment. The cells were cultured in MS medium containing 0.7 mg/L 2,4-D, 0.3 mg/L kinetin, 30 g/L sucrose and 200 mM NaCl at $25^{\circ}C$ in the light (100 rpm). Dykellic acid strongly inhibited the cell growth by evaluating the cell fresh wt and the ion conductivity in the medium ($IC_{50}$/, about 20 $\mu$M). The results as inhibition of cell growth and cell wall damage were same. The compound significantly increased the protein contents and the SOD specific activity in proportion with the dosage. The results suggested that dykellic acid may have biological activity in plant cells and tobacco PM cells may be suitable biomaterials for in vitro evaluation of the biological activity of natural products.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.10
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• pp.1674-1682
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• 2020

Objective: This study aimed to elucidate the effect of miR-140 on the proliferation of porcine fetal fibroblasts (PFFs) and identify the target genes of miR-140 in PFFs. Methods: In this study, bioinformatics software was used to predict and verify target genes of miR-140. Quantitative polymerase chain reaction and western blot were used to detect the relationship between miR-140 and its target genes in PFFs. Dual luciferase reporter gene assays were performed to assess the interactions among miR-140, type 1 insulin-like growth factor receptor (IGF1R), and SRY-box 4 (SOX4). The effect of miR-140 on the proliferation of PFFs was measured by CCK-8 when PFFs were transfected with a miR-140 mimic or inhibitor. The transcription factor SOX4 binding to promoter of IGF1R was detected by chromatin immunoprecipitation assay (ChIP). Results: miR-140 directly targeted IGF1R and inhibited proliferation of PFFs. Meanwhile, miR-140 targeted transcription factor SOX4 that binds to promoter of porcine IGF1R to indirectly inhibit the expression of IGF1R. In addition, miR-140 inhibitor promoted PFFs proliferation, which is abrogated by SOX4 or IGF1R knockdown. Conclusion: miR-140 inhibited PFFs proliferation by directly targeting IGF1R and indirectly inhibiting IGF1R expression via SOX4, which play an important role in the development of porcine fetal.

• Biomedical Science Letters
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• v.11 no.3
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• pp.355-363
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• 2005

This study aimed to investigate the cerebroprotective effect of vascular endothelial growth factor (VEGF) on permanent focal cerebral ischemia in Sprague-Dawley rats. Right middle cerebral artery (MCA) was occluded for 6 and 24 hours by an intraluminal monofilament technique. An open cranial window was made on the right parietal bone for determination of continuous changes in regional cerebral blood flow (rCBF) by laser-Doppler flowmetry. The infarct size was morphometrically determined using the 2,3,5-triphenyltetrazolium chloride technique. Brain edema was determined by measuring brain water content. In normal rats, rCBF was significantly increased by intravenous infusion of VEGF for 10 minutes. The VEGF-induced increase in rCBF was significantly inhibited by pretreatment with suramin, a heparin-binding growth factor inhibitor as well as $N^{\omega}-nitro-L-arginine$, a nitric oxide synthase inhibitor. In focal cerebral ischemic rats, the amplitude of decrease in rCBF during ischemic period was significantly less in VEGF-treated group, compared with that in vehicle-treated group. The cerebral infarct size was reduced by VEGF in a dose-dependent manner. The brain edema formation was dose-dependently reduced by VEGF in 24-hour MCA occlusion group but not in 6-hour MCA occlusion group. It is suggested that VEGF not only improves the rCBF during cerebral ischemic period but also reduces the brain edema formation, and thereby exert a protective effect on focal cerebral ischemia in rats.

• Journal of the Korean GEO-environmental Society
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• v.13 no.4
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• pp.5-11
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• 2012

Acid mine drainage (AMD) is one of the most severe environmental problem that results from the oxidation of pyrite $(FeS_2)$ and various other metal sulfides. In this study, the influence of microorganism was tested on the process where AMD was released and the method to inhibit AMD generated by microorganisms at abandoned mine area. The activity and growth rate of Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans, common microorganisms affecting AMD occurrence, were measured. Chlorine dioxide $(ClO_2)$, NaCl, or surfactant (ASOR-770) was used as an inhibitor for working on activity and growth of microorganism. Among the three inhibitors, 10ppm of chlorine dioxide was the most effective inhibitor for AMD control due to the reduced the activity and growth of microorganisms by 20%.