• Journal of Plant Biology
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• v.38 no.4
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• pp.343-348
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• 1995

Treatment of Pisum sativum tissue with the protein kinase inhibitor staurosphorine resulted in impairment of 3H-indoleacetic acid transport in etiolated stem segments. The transport inhibitiion was accompanied by an increase in net uptake of labeled auxin in the tissue. The magnitude of auxin accumulation in tissue treated with the phytotropin N-1-naphthylphthalaic acid (NPA) which specifically blocks the efflux of auxin in the plasma membrane was reduced by the protein kinase inhibitor, suggesting that inhibition of protein phosphorylation could lead to hindrance of the auxin-exporting function of NPA receptors. The flavonoid genistein which is also known to inhibit protein kinase likewise reduced NPA-induced auxin accumulation. However, the flavonoid did not bring about auxin accumulation by itself, nor did it inhibit auxin transport. In view of the finding that the flavonoid also competes with NPA for a common binding site, a mechanism for the flavonoid effect on the NPA action will be proposed.

• Genomics & Informatics
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• v.21 no.3
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• pp.43.1-43.13
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• 2023

Melanin is synthesized by tyrosinase to protect the skin from ultraviolet light. However, overproduction and accumulation of melanin can result in hyperpigmentation and skin melanoma. Tyrosinase inhibitors are commonly used in the treatment of hyperpigmentation. Natural tyrosinase inhibitors are often favoured over synthetic ones due to the potential side effects of the latter, which can include skin irritation, allergies, and other adverse reactions. Nuciferine, an alkaloid derived from Nelumbo nucifera, exhibits potent antioxidant and anti-proliferative properties. This study focused on the in silico screening of nuciferine for anti-tyrosinase activity, using kojic acid, ascorbic acid, and resorcinol as standards. The tyrosinase protein target was selected through homology modeling. The residues of the substrate binding pocket and active site pockets were identified for the purposes of grid box optimization and docking. Therefore, nuciferine is a potent natural tyrosinase inhibitor and shows promising potential for application in the treatment of hyperpigmentation and skin melanoma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.167-173
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• 2005

To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

• Journal of Microbiology and Biotechnology
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• v.10 no.5
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• pp.707-713
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• 2000

Myasthenia gravis (MG) is caused mainly by autoantibodies directed against acetylcholine receptors located in the postsynaptic muscle cell membrane. Using in vitro selection techniques, we isolated an RNA containing 2'-fluoro pyrimidines that can specifically and avidly ($K_d$ ~25 nM) bind rat monoclonal antibody called mAb198, which recognizes the main immunogenic region on the acetylcholine receptors. This RNA can act as a very effective decoy and block mAb198 binding to the receptors in vitro. Furthermore, this RNA decoy can prevent the antigenic modulation of the acetylcholine receptor caused by mAb198 in human muscle cell cultures with and $IC_{50} $of approximately $2.4{\mu}M$. These results indicate that the RNA selected in this study is a more potent decly inhibitor of myashthenic antibodies than the previously identified RNA with 2'-amino pyrimidines [11]. Moreover, this RNA cross-reacts with autoantibodies from patients with MG and can protect human cells from the effects of these antibodies. These observations have important implications for developing an antigen-specific treatment of autoimmune diseases including MG, which is based on decoy RNAs selected in vitro.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.354-361
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• 2017

Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation. The LPA1 receptor inhibitor Ki16425 blocked LPA responses in MSCs. Although TAZ knockdown or knockout did not reduce LPA-induced phosphorylation of ERK and AKT, the MEK inhibitor U0126 or the ROCK inhibitor Y27632 blocked LPA-induced TAZ expression along with the reduction in the proliferation and migration of MSCs. Our data suggest that TAZ is an important mediator of LPA signaling in MSCs in the downstream of MEK and ROCK signaling.

• Molecules and Cells
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• v.23 no.2
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• pp.138-144
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• 2007

Previously we showed that the human GM3 synthase gene was expressed during the induction of megakaryocytic differentiation in human leukemia K562 cells by phorbol 12-myristate 13-acetate (PMA). In this study we found that treatment of PMA-induced K562 cells with $G{\ddot{o}}6976$, a specific inhibitor of PKC, and U0126, an inhibitor of the extracellular signal-regulated kinase (ERK) reduced expression of GM3 synthase, whereas wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K) did not. Moreover, activation of ERK and cAMP response element binding protein (CREB) was prevented by pretreatment with $G{\ddot{o}}6976$ and U0126. PMA stimulated the promoter activity of the 5'-flanking region from -177 to -83 region of the GM3 synthase gene, and mutation or deletion of a CREB site located around -143 of the promoter reduced PMA-stimulated promoter activity, as did the inhibitors $G{\ddot{o}}6976$ and U0126. Our results demonstrate that induction of GM3 synthase during megakaryocytic differentiation in PMA-stimulated human leukemia K562 cells depends upon the PKC/ERK/CREB pathway.

• YAKHAK HOEJI
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• v.52 no.2
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• pp.111-116
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• 2008

Diethylstilbestrol (DESB) is a synthetic estrogen not only that routinely prescribed, but also that known to be a teratogen. In this study, we found a novel pharmacological feature that DESB is able to positively modulate CD29 $({\beta}1-integrin)$ function. Thus, DESB up-regulated homotypic cell-cell adhesion of monocytic U937 cells mediated by CD29. However, DESB did not increase the surface level of CD29 and its binding activity to ligand (fibronectin), according to flow cytometric analysis and cell-fibronectin adhesion assay. Instead, the DESB-mediated up-regulation of cell-cell adhesion was blocked by several signaling enzyme inhibitors. Treatment of U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SB20358 (a p38 inhibitor) or Rp-8-pCPT-cGMP (a protein kinase G inhibitor) clearly inhibited DESB-mediated up-regulation of cell-cell adhesion induced by CD29. However, estrogen receptor antagonist ICI 182,780 failed to abrogate DESB effect. Therefore, our data suggest that DESB may up-regulate CD29-mediated cell-cell adhesion via modulating intracellular signaling enzymes such as ERK, PKG, and p38, independent of estrogen receptor function.

• International journal of thyroidology
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• v.11 no.2
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• pp.172-175
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• 2018

Anti-programmed cell death-1 (PD-1) humanized monoclonal antibody inhibits PD-1 activity by binding to the PD-1 receptor on T-cells and blocking PD-1 ligands and induces immune tolerance of cancer cells. It has been widely used for various kinds of cancer treatment. However, many immune-related adverse events (irAEs) have been reported because it modulates our immune system. In this case study, we reported a case of 42-year-old woman with Hashimoto's thyroiditis who showed rapid aggravation of thyroid goiter and acute hyperventilation syndrome after treatment with PD-1 inhibitor as a neoadjuvant chemotherapy for breast cancer.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1810-1818
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• 2020

Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against pro-inflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL-17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.

• BMB Reports
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• v.56 no.11
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• pp.606-611
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• 2023

The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of viral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target the active site for substrate binding. Mpro exists as a dimer, which is essential for its activity. We investigated the potential of the Mpro dimer interface to act as a drug target. The dimer interface is formed of domain II and domain III of each protomer, in which N-terminal ten amino acids of the domain I are bound in the middle as a sandwich. The N-terminal part provides approximately 39% of the dimer interface between two protomers. In the real-time fluorometric turn-on assay system, peptides of the N-terminal ten amino acids, N10, can inhibit the Mpro activity. The dimer interface could be a prospective drug target against Mpro. The N-terminal sequence can help develop a potential inhibitor.