• Korean Journal of Veterinary Research
• /
• v.49 no.1
• /
• pp.1-8
• /
• 2009

The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.

• Journal of Microbiology
• /
• v.43 no.6
• /
• pp.529-536
• /
• 2005

Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing $\alpha-mannosidase-like$ protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.

• Applied Biological Chemistry
• /
• v.21 no.3
• /
• pp.197-203
• /
• 1978

In order to investigate mechanisms related to the microbial degradation of 3,4-dichloroaniline, it was incubated with a soil fungus, Chaetomium globosum and the following results were obtained. (1) 3,4-Dichloroacetanilide turned out to be the major metabolite, indicating that acetylation is the major scheme. (2) The presence of trace amounts of 3,4-dichloronitrobenzene, 3,3', 4,4'-tetrachloroazo-benzene, 3,4-dichloroaniline is suggestive of the aromatic amine oxidation as the minor pathway. (3) Other metabolites with m/e 112, 114, and 279 were also isolated, but their identities are under investigation. (4) Dechlorination occurring during incubation indicates the possibility of forming hydroxylated and other metabolites.

• International Journal of Advanced Culture Technology
• /
• v.7 no.4
• /
• pp.125-136
• /
• 2019

The radish skin and radish greens are an edible part of the radish. But they are removed before eating the radish and used as a byproduct or an animal feed material because of their tough and rough texture. Melanin is a pigment that gives colour to our skin. But increased production of melanin can turn into benign or malignant tumours. These days due to global warming, the amount of Ultra violet (UVB) rays has been extensively increased with sunlight. Due to this, a phenomenon called exogenous photo aging is widely observed for all skin colour and types. As a result of this phenomenon, a set of enzymes called matrix metalloproteinases (MMP's) that serves as degradation enzymes for extracellular matrix proteins mainly collagen is increased, causing depletion in collagen and resulting in early wrinkles formation. Therefore in our study we used the murine melanoma cell line B16/F10 to study the melanogenesis inhibition by Heated radish extract (HRE) in vitro and we used HRM-2 hair less mice exposed to artificial UVB for checking the efficacy of Heated radish extract in vivo. Furthermore, we prepared a 3% Heated radish extract (HRE) cream and checked its effects on human skin. Our results have clearly demonstrated that Heated radish extract (HRE) have potently suppressed the tyrosinase activity and melanin production in B16/F10 cells. It had also reduced the expression of components involved in melanin production pathway both transcriptionally and transitionally. In in vivo studies, HRE had potently suppressed the expression of MMP's and reduced the wrinkle formation and inhibited collagen degradation. Moreover, on human skin, ginseng cream increased the resilience, skin moisture and enhanced the skin tone. Therefore in light of these findings, we conclude that HRE is an excellent skin whitening and antiaging product.

• Journal of Microbiology
• /
• v.33 no.3
• /
• pp.208-214
• /
• 1995

The effects of various 2, 4-D-degradative plasmids on the axenic growth patterns, the degradation phenotypes, and the competitiveness of different host bacteria were evaluated in liquid cultures; the organisms and plasmids used were Alcaligenes eutrophus JMP134/pJP4, Alcaligenes paradoxus/p2811, Pseudomonas pickettii/p712, pJP4, and p712 or p 2811 exhibited very different restriction fragment profiles in restriction endonuclease digests. These plasmids were transferred to the recipients (P. cepacia and Alcaligenes JMP228) at relatively high frequencies ranging from 8.9 $\times$ 10$^3$ to 1.6 $\times$ 10$^5$ per donar cell. In the axenic liquid cultures the fast-growing strains, such as P. pseudomallei/p745 and P. cepacia/pJP4, exhibited short lag periods, high specific growth rates, and high relative fitness coefficients, while the slow-growing strains, such as P. pickettii/p712 and A. paradoxus/p2811, had long lag periods, low specific growth rates, and low relative fitness coefficients. Depending on the type of plasmid containing the genes for the 2, 4-D pathway, some transconjugants exhibited intermediate grwoth patterns between the fast-growing strains and the slow-growing strains. The plasmid and plasmid-host interactions determined specific growth rate and lag time, respectively, which were shown to be principal determinants of competitiveness among the strains, but relative fitness coefficient derived from the axenic culture was not always predictive for the mixed culture condition.

• Restorative Dentistry and Endodontics
• /
• v.31 no.3
• /
• pp.203-214
• /
• 2006

Dental pulp is a loose, mesenchymal tissue almost entirely enclosed in the dentin. It consists of cells, ground substance, and neural and vascular supplies. Damage to the dental pulp by mechanical, chemical, thermal, and microbial irritants can provoke various types of inflammatory response. Pulpal inflammation leads to the tissue degradation, which is mediated in part by Matrix metalloproteinase leads to accelerate extracellular matrix degradation with pathological pathway We have now investigated the induction of MMPs and inflammatory cytokines by Lipopolysaccharide (LPS) control of inflammatory mediators by peroxisome proliferator-activated receptors (PPARs). Human dental pulp cells exposed to various concentrations of LPS ($1-10{\mu}g/ml$) revealed elevated levels of MMP-2 and MMP-9 at 24 hrs of culture. LPS also stimulated the production of ICAM-1, VCAM-1, $IL-1{\beta},\;and\;TNF-{\alpha}$. Adenovirus $PPAR{\gamma}\;(Ad/PPAR{\gamma})\;and\;PPAR{\gamma}$ agonist rosiglitazone reduced the synthesis of MMPs, adhesion molecules and pro-inflammatory cytokines. The inhibitory effect of $Ad/PPAR{\gamma}$ was higher than that of $PPAR{\gamma}$ agonist. These result offer new insights in regard to the anti-inflammatory potential of $PPAR{\gamma}$ in human dental pulp cell.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.7
• /
• pp.999-1010
• /
• 2021

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment. They are highly toxigenic and carcinogenic. Probiotic bacteria isolated from fermented foods were tested to check their ability to degrade and/or detoxify PAHs. Five probiotic bacteria with distinct morphologies were isolated from a mixture of 26 fermented foods co-cultured with benzo(a)pyrene (BaP) containing Bushnell Haas minimal broth. Among them, B. velezensis (PMC10) significantly reduced the abundance of BaP in the broth. PMC10 completely degraded BaP presented at a lower concentration in broth culture. B. velezensis also showed a clear zone of degradation on a BaP-coated Bushnell Haas agar plate. Gene expression profiling showed significant increases of PAH ring-hydroxylating dioxygenases and 4-hydroxybenzoate 3-monooxygenase genes in B. velezensis in response to BaP treatment. In addtion, both live and heat-killed B. velezensis removed BaP and naphthalene (Nap) from phosphate buffer solution. Live B. velezensis did not show any cytotoxicity to macrophage or human dermal fibroblast cells. Live-cell and cell-free supernatant of B. velezensis showed potential anti-inflammatory effects. Cell-free supernatant and extract of B. velezensis also showed free radical scavenging effects. These results highlight the prospective ability of B. velezensis to biodegrade and remove toxic PAHs from the human body and suggest that the biodegradation of BaP might be regulated by ring-hydroxylating dioxygenase-initiated metabolic pathway.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.11
• /
• pp.1559-1567
• /
• 2021

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed β-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of β-catenin. In addition, MRBE repressed the expression of the β-catenin/T-cell factor (TCF)-dependent genes, c-myc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin VFITC-positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular β-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of β-catenin and may have significant chemopreventive potential against MM.

• Journal of Ginseng Research
• /
• v.48 no.1
• /
• pp.40-51
• /
• 2024

Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-kB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway. Materials and methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on KIF20A expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as in vitro and in vivo cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining. Results: KIF20A is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth in vitro and in vivo. Ginsenoside Rg3 can suppress the transcription of KIF20A. GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (β-TrCP1), a substrate recognition subunit for SCF^β-TrCP E3 ubiquitin ligase. In vitro ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates KIF20A overexpression-induced CDC25A upregulation. Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit KIF20A transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.

• Korean Journal of Ecology and Environment
• /
• v.34 no.1 s.93
• /
• pp.54-61
• /
• 2001

Changes in methanogenic pathway at low temperature were studied by incubation experiments of sediment slurries from the littoral zone of Reservoir Paldang. Methane production rates in sediment slurries increased exponentially between $5＾{\circ}C$and $45＾{\circ}C$, reached a maximum rate of $7.4\;nmol\;{\cdot}\;g^{-1}\;{\cdot}\;h^{-1}$ at $45＾{\circ}C$, and then declined to low rate. The shift of incubation temperature from high temperature ($30＾{\circ}C$) to lowtemperature ($15＾{\circ}C$) resulted in a decrease of methane production rate and of hydrogen accumulation rate, and the transient accumulation of acetate concentration. Chlorofarm inhibited perfectly methanogenesis and resulted in the accumulation of hydrogen and acetate as immediate precursors for metltane formation at both incubation temperatures of $15＾{\circ}C$ and $30＾{\circ}C$. In terms of equivalent methane which was calculated from the two intermediary metabolites accumulated in absence of methanogenesis, methane production from acetate was accounted for 14% of total methanogenesis at $30＾{\circ}C$ and 75% at $15＾{\circ}C$, respectively. When the high acetate concentrations above 19 mM were added to sediment slurries, methane production was inhibited at the low temperature ($15＾{\circ}C$) . Our results demonstrate that contribution of acetate on methanogenesis increases at low temperature, but this pathway is inhibited by high concentration of acetate. Therefore acetate-utilizing methanogensis appears to be a key reaction at low temperature, and seems to be one of bottlenecks of the low temperature anaerobic degradation of organic matter in littoral sediments of the reservoir.