• Molecules and Cells
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• v.44 no.1
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• pp.13-25
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• 2021

Apoptosis and compensatory proliferation, two intertwined cellular processes essential for both development and adult homeostasis, are often initiated by the mis-regulation of centrosomal proteins, damaged DNA, and defects in mitosis. Fly Anastral spindle 3 (Ana3) is a member of the pericentriolar matrix proteins and known as a key component of centriolar cohesion and basal body formation. We report here that ana3m19 is a suppressor of lethality induced by the overexpression of Sol narae (Sona), a metalloprotease in a disintegrin and metalloprotease with thrombospondin motif (ADAMTS) family. ana3m19 has a nonsense mutation that truncates the highly conserved carboxyl terminal region containing multiple Armadillo repeats. Lethality induced by Sona overexpression was completely rescued by knockdown of Ana3, and the small and malformed wing and hinge phenotype induced by the knockdown of Ana3 was also normalized by Sona overexpression, establishing a mutually positive genetic interaction between ana3 and sona. p35 inhibited apoptosis and rescued the small wing and hinge phenotype induced by knockdown of ana3. Furthermore, overexpression of Ana3 increased the survival rate of irradiated flies and reduced the number of dying cells, demonstrating that Ana3 actively promotes cell survival. Knockdown of Ana3 decreased the levels of both intra- and extracellular Sona in wing discs, while overexpression of Ana3 in S2 cells dramatically increased the levels of both cytoplasmic and exosomal Sona due to the stabilization of Sona in the lysosomal degradation pathway. We propose that one of the main functions of Ana3 is to stabilize Sona for cell survival and proliferation.

• Nutrition Research and Practice
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• v.5 no.5
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• pp.375-380
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• 2011

This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol$/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 ${\mu}mol$/L within 48 h. Inorganic sulfur significantly decreased cell motility and invasion in the MDA-MB-231 cells in a dose-dependent manner (P<0.05), as determined using a Boyden chamber assay and a Matrigel chamber. The activities of MMP-2 and MMP-9 were significantly reduced by inorganic sulfur in a dose-dependent manner (P<0.05). The inorganic sulfur also significantly inhibited MMP-2 and MMP-9 expression in the cells (P<0.05). These data suggest that inorganic sulfur can suppress cancer cell motility and invasion by inhibiting MMP-2 and MMP-9 activity and gene expression in MDA-MB-231 cells.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.168.3-169
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• 2003

The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. Tissue inhibitor of metalloprotease (TIMP)-2, an endogenopus inhibitor of MMP-2, has been shown to inhibit invasion and metastasis. We have previously shown that MMP-2 is responsible for the H-ras-induced invasive and migrative phenotypes in MCF10A human breast epithelial cells. Here, we investigated the effect of TlMP-2 overexpression on invasion and migration in H-ras MCF10A cells. (omitted)

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.241-246
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• 2004

To develop novel anti-aging peptides from the germinated black rice, we treated with bromelain, papain and Pronase E. And we investigated the effects of the germinated black rice peptide (GBRP) as anti-aging cosmetic ingredients, and compared with the non-germinated black rice protein (NBRP). We investigated the effects on in vitro inhibition of matrix-metalloprotease (MMP), proliferation of human skin fibroblasts, stimulation of collagen synthesis and expression of UVA-induced MMPs in human skin fibroblasts, UVA induced MMP-1 expression and collagen contents in human skin fibroblasts were analyzed by enzyme-linked immunosorbent assay (ELISA). As a result, the molecular weight distributions of GBRP and NBRP were determined by gel permeation chromatography to be approximately 900 and 10,000 daltons. GBRP increased skin cell proliferation about 40% and reduced UVA-induced MMP-1 expression about 50%. Also the collagen protein level of cells, which were cultured with GBRP, was increased about 25%. These results suggest that the geminated plant seed peptides can be novel anti-aging ingredients for cosmetics.

• Journal of Life Science
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• v.29 no.11
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• pp.1192-1199
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• 2019

The intention of this study was to confirm the possible use of an ethanol extracts of Nelumbinis Rhizomatis Nodus (NRN) as a cosmetic material. To this end, we extracted NRN with 70% ethanol and performed biological activity evaluation of whitening efficacy and wrinkle reduction. We performed cellular tyrosinase inhibition and melanin contents assay to check the whitening activity of NRN and carried out a toxicity evaluation of NRN via an MTT assay and the amounts of associated proteins that affect melanin production in a melanoma cell line (B16F10). And collagenase inhibitory assay was performed for the evaluation of anti-wrinkle of samples. In addition, a toxicity evaluation using an MTT assay and matrix metalloprotease (MMP-1) and procollagen synthesis inhibition by NRN were evaluated in a fibroblast cell line (CCD-986sk). Western blot results for the whitening activity evaluation revealed that the levels of two proteins related to melanin production, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2), were decreased in a dose-dependent manner. Moreover, collagenase inhibition activity at a concentration of $500{\mu}g/ml$ NRN by measuring epigallocatechin-3-gallate (EGCG) was increased by more than 80% compared to the control group. Meanwhile, procollagen synthesis was reduced by 68.8% in the UVB-induced CCD- 986sk cells group whereas collagen synthesis recovered by 80.2% with $25{\mu}g/ml$ NRN. The MMP-1 expression rate showed 20.2% reduction at $25{\mu}g/ml$. The results of the experiments verified the whitening and wrinkle suppression effects of NRN and confirmed that it could be used as a safe natural cosmetic material in the future.

• Biomedical Science Letters
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• v.19 no.1
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• pp.9-16
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• 2013

Elevated blood triglyceride (TG) levels correlate with development of atherosclerosis suggesting that TG may promote the development of this disease. During atherosclerosis, TG is taken up by tissue macrophages which result in dramatic changes in various secreted factors. One such factor is the family of matrix metalloproteases (MMP) which are involved in tissue remodeling during both physiological and pathological processes. In this study, we examined the MMP expression profile in PMA-differentiated THP-1 macrophages treated with TG. We found that TG-treated THP-1 macrophages showed decreased expression of MMP-3, MMP-7, MMP-8 and MMP-9 in a time- and dose-dependent manner. In contrast, expression of MMP-1, MMP-2, and MMP-10 remained relatively unchanged after TG treatment. In addition, we found that expression of select MMPs was affected by various inhibitors of signaling pathways. In particular, expression of MMP-3 was slightly recovered by cRAF and PLC signaling pathway inhibitors. These data suggests a possible role of MMPs in macrophages during TG-induced atherosclerosis.

• Journal of Life Science
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• v.22 no.12
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• pp.1600-1607
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• 2012

The matrix metalloproteinase (MMP) family plays essential roles in physiological processes such as embryonic development, angiogenesis, wound healing, and tissue homeostasis as a consequence of MMPr capacity for breaking down many types of extracellular matrix proteins. Imbalanced regulation of MMP expression can also lead to pathological conditions such as tumor progression. We recently reported that the Drosophila Mmp1 gene is highly expressed in the digestive tract and is required for the maintenance of intestinal homeostasis such as by restriction of uncontrolled intestinal stem cell proliferation. However, the regulatory mechanisms of MMP gene expression in the intestine remain unclear. In this study, we determined that the expression of Mmp1 is regulated by the homeodomain transcription factor Caudal. Experiments using the targeted expression of Caudal under the regulation of Gal4-UAS system indicated that endogenous Caudal is required for the Mmp1 gene expression in the adult Drosophila intestine and that exogenous Caudal induces Mmp1 expression. Transient transfection experiments indicated that Caudal can activate the promoter activity of Mmp1 and that several putative Caudal binding sites in the 5'-flanking region of the Mmp1 gene may be critical to the upregulation by Caudal. Our data suggest that Mmp1 is one of the target genes of Caudal in physiological normal condition and in tumorigenesis.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.90-90
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• 2018

Kochiae Fructus is a medicinal plant used as medicine of the urinary organs, skin disease and inflammation. In this study, anti-inflammatory activity of Kochiae Fructus extract and its possible mechanisms of action were examined. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO), pro-inflammatory cytokine production and matrix metalloprotease-9 (MMP-9) in murine macrophage-like cell line Raw 264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK and MAPK and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 were investigated by Wesern blot analysis. The extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. As a result, we suggest that the extract of Kochiae Fructus decreased the production of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6), nitric oxide, MMP-9 in LPS-induced Raw264.7 cells. Kochiae Fructus has possibility to be used as therapeutic benefits against inflammatory diseases.

• Journal of Korean Neurosurgical Society
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• v.53 no.6
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• pp.323-330
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• 2013

Objective : To develop a simple, reproducible model of disc degeneration in rabbits through percutaneous annular puncture and to confirm the degree of degeneration over time. Methods : Fifteen New Zealand white rabbits (4 to 5 months old and weighing approximately 3 to 3.5 kg each) underwent annular puncture of the L2-L3, L3-L4, and L4-L5 discs. Rabbits were sacrificed at 4, 8, or 20 weeks after puncture. For a longitudinal study to assess changes in disc height over time, serial X-rays were performed at 0, 2, 4, 8, and 20 weeks for rabbits in the 20-week group. Upon sacrifice, the whole spinal column and discs were extracted and analyzed with magnetic resonance imaging (MRI), real time reverse transcriptase-polymerase chain reaction, and histological staining. Results : The X-rays showed a slow, progressive decrease in disc height over time. Significant disc space narrowing compared to preoperative disc height was observed during the time period (p<0.001). The MRI grade, aggrecan, and matrix metalloprotease-13 mRNA expression and hematoxylin and eosin/safranin O/anti-collagen II staining were consistently indicative of degeneration, supporting the results of the X-ray data. Conclusion : Percutaneous annular puncture resulted in slow, reproducible disc degeneration that was confirmed by radiology, biochemistry, and histology. This in vivo model can be used to study and evaluate the safety and efficacy of biologic treatments for degenerative disc disease.

• BMB Reports
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• v.56 no.8
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• pp.439-444
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• 2023

Emphysema is a chronic obstructive lung disease characterized by inflammation and enlargement of the air spaces. Regorafenib, a potential senomorphic drug, exhibited a therapeutic effect in porcine pancreatic elastase (PPE)-induced emphysema in mice. In the current study we examined the preventive role of regorafenib in development of emphysema. Lung function tests and morphometry showed that oral administration of regorafenib (5 mg/kg/day) for seven days after instillation of PPE resulted in attenuation of emphysema. Mechanistically, regorafenib reduced the recruitment of inflammatory cells, particularly macrophages and neutrophils, in bronchoalveolar lavage fluid. In agreement with these findings, measurements using a cytokine array and ELISA showed that expression of inflammatory mediators including interleukin (IL)-1β, IL-6, and CXCL1/KC, and tissue inhibitor of matrix metalloprotease-1 (TIMP-1), was downregulated. The results of immunohistochemical analysis confirmed that expression of IL-6, CXCL1/KC, and TIMP-1 was reduced in the lung parenchyma. Collectively, the results support the preventive role of regorafenib in development of emphysema in mice and provide mechanistic insights into prevention strategies.