• Clinical and Experimental Reproductive Medicine
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• v.22 no.2
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• pp.191-201
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• 1995

Transcriptional activation of the embryonic genome initiates at 2-cell stage in mouse embryo and is characterized by the synthesis of TRC which is restricted to 2-cell stage. To investigate the roles of various protein kinases on the embryonic gene activation, the effects of protein kinase inhibitors on in vitro development and protein synthetic profiles of the early mouse embryos were examinded. None of ${\alpna}-amanitin$ which is a mRNA synthetic inhibitor, H8 which is a PKA inhibitor, and H7 which is a PKC inhibitor, affected on first cleavage of mouse 1-cell embryos in vitro. However, all of these drugs inhibited the second cleavage. When the drugs were removed following treatment for 6 hours, H8 or H7 treatment showed little inhibition on subsequent development of 1-cell embryos to 2-cell stage or further. In contrast, ${\alpna}-amanitin$ irreversibly inhibited the development of 1-cell embryos to 2-cell stage following removal of the drug. Genistein, a TPK inhibitor, inhibited both the first cleavage of 1-cell embryos and the second cleavage of 2-cell embryos, suggesting that TPK activity may be important during the early cleavages. All of the above four drugs inhibited TRC synthesis as shown by the fluorographic analysis of $[^{35}S]-Met$ labeled protein profiles. When late 1-cell embryos were treated with H7 and analyzed synthetic patterns of $[^{35}S]-Met$ labeled protein, the quantitative differences of protein synthesis on SDS-PAGE appeared on 77 kD and 33 kD region at $32{\sim}38$ hours post hCG. From these studies, transcriptional activation of embryonic genome is not essenting to the mouse 1-cell embryos to develop to 2-cell stage. Hawever, TPK activity is reguisite for both the first cleavage and second cleavage. Similarly, both PKC and PKA activities are required for the second cleavage of mouse embryos, but not for the first cleavage.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4393-4398
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• 2013

Background: Chromosomal translocations are genetic aberrations associated with specific non-Hodgkin lymphoma (NHL) subtypes. This study investigated the differential gene expression profile of Egyptian NHL cases based on a microarray approach. Materials and Methods: The study included tissue samples from 40 NHL patients and 20 normal lymph nodes used as controls. Total RNA was extracted and used for cDNA microarray assays. The quantitative real time polymerase chain reaction was used to identify the aberrantly expressed genes in cancer. Results: Significant associations of 8 up-regulated and 4 down-regulated genes with NHL were observed. Aberrant expression of a new group of genes not reported previously was apparent, including down-regulated NAG14 protein, 3 beta hydroxy-delta 5-c27 steroid oxi-reductase, oxi-glutarate dehydrogenase (lipo-amide), immunoglobulin lambda like polypeptide 3, protein kinase x linked, Hmt1, and caveolin 2 Tetra protein. The up-regulated genes were Rb binding protein 5, DKFZP586J1624 protein, protein kinase inhibitor gamma, zinc finger protein 3, choline ethanolamine phospho-transferase CEPT1, protein phosphatase, and histone deacetylase-3. Conclusions: This study revealed that new differentially expressed genes that may be markers for NHL patients and individuals who are at high risk for cancer development.

• Biomedical Science Letters
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• v.17 no.4
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• pp.291-295
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• 2011

PD98059 is the specific inhibitor of extracellular signaling-regulated kinase (ERK) kinase (MEK). ERK is involved in a mitogen-activated protein kinase (MAPK) cascade controlling cell growth and differentiation. Although the inhibition of ERK is known to induce cell death in various cell lines, this effect is still controversial and the role of PD98059 on the death of HeLa $S_3$ cells, a subclone of the cervical cancer cell line, is not well understood. The apoptosis of HeLa $S_3$ cells increased after the treatment of 50 ${\mu}M$ PD98059. The induction of apoptosis by PD98059 was occurred in a time- and a dose-dependent manners. The expression of Bcl-2 was reduced in accordance with decrease of ERK2 expression. Taken together, these results indicate that PD98059 has a cytotoxicity in HeLa $S_3$ cells and it may be used as a potential target for the treatment of cervical cancer.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.166.1-166.1
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• 2003

Autotaxin (ATX) is a 125-kDa glycoprotein and a strong motogen that can increase invasiveness and angiogenesis, originally isolated from the conditioned medium of human melanoma A2058 cells. And it is a strong. Recently, we suggested that ATX promotes motility via G protein-coupled PI3K$\gamma$, and Cdc42/Racl are essential for ATX-induced tumor cell motility in A2058 melanoma cells. In the present study, we found that activation of p21-activated kinase1 (PAK1) was required for ATX-induced cell motility. (omitted)

• The Journal of Korean Medicine
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• v.21 no.4
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• pp.193-203
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• 2000

Objectives : Hindered barrier function of vascular endothelium has been implicated in the initiation and progression of degenerative vascular diseases such as atherosclerosis. In this study, the effect of Sunghyangchungisan(SHCS) as a protectant against oxidant-induced destruction of endothelial barrier function was assessed. Methods : Toward this end, endothelial cells derived from the human umbilical vein were cultured as monolayers on permeable membrane filters. Endothelial permeability was monitored by measuring transendothelial electrical resistance and movement of low density lipoprotein (LDL) across the endothelial monolayer. Results : Along with increased movement of LDL, $H_2O_2$-induced increase in endothelial permeability was paralleled by a decrease in transendotheliaI electrical resistance. The effect of $H_2O_2$ was mimicked by phorbol 12-myristate 13-acetate (PMA), a potent activator of proteinkinase C. Calphostin-C, a protein kinase C inhibitor, effectively blocked the increase in endothelial permeability induced by $H_2O_2$ or PMA, indicating that activation of protein kinase C is associated with the $H_2O_2-induced$ permeability change. SHCS effectively protected the endothelial monolayer against $H_2O_2-induced$ increase in permeability, whereas, it did not affect PMA-induced change. Forskolin, a potent activator of adenylyl cyclase, antagonized $H_2O_2$ to increase endothelial permeability. In addition, in ${H_2O_2}-treated$ cens, intracenular cAMP concentration was significantly decreased, indicating that impaired cAMP production as well as activation of proteinkinase C is a mechanism underlying ${H_2O_2}>-induced$$H_2O_2$ with regard to its effect on intracellular cAMP content. However, SHCS itself did not affect resting cAMP concentration in endothelial cells. Conclusions : These results suggest that SHCS might operate as an effective protectant against oxidant-induced destruction of endothelial barrier function. The mechanism does not appear to involve direct interaction with protein kinase C- or cAMP-associated signaling mechanism.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.2
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• pp.119-128
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• 2023

Purpose : The fruit of Actinidia polygama has been used in oriental medicine for the treatment of gout, rheumatoid arthritis, and inflammation. Though A. polygama exhibited anti-inflammatory activity in RAW 264.7 cells and carrageenan-induced rat paw edema, the exact mechanism for anti-inflammation was not evaluated yet. In this study, the anti-inflammatory mechanisms of A. polygama ethanol extract (APEE) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Methods : WST-1 assay was applied to analyze the cytotoxic effect of APEE in RAW 264.7 cells. The productions of nitric oxide (NO) and prostaglandin (PG) E₂ were analyzed by the Griess reaction and enzyme immunoassay (EIA) assay, respectively. In addition, protein expressions for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured by Western blot analysis. The activated status of an inflammatory transcription factor, NF-κ B, and its upstream signaling molecules, mitogen-activated protein kinases (MAPKs), was also evaluated by Western blot analysis. Results : As a result, APEE treatment did not exhibit any cytotoxicity until the concentration of 200 ㎍/㎖. APEE treatment significantly inhibited NO and PGE₂ productions as well as their enzymes, iNOS and COX-2 in a dose-dependent manner. The inflammatory transcription factor, NF-κ B, was also attenuated by APEE treatment. In addition, the phosphorylated status of MAPKs such as extracellular regulated kinase (ERK), c-jun NH2 kinase (JNK), and p38, were significantly diminished by APEE treatment in LPS stimulated RAW 264.7 cells. Conclusion : Consequently, APEE treatment significantly attenuated the production of inflammatory mediators and their enzyme expressions in LPS-stimulated RAW 264.7 cells. The inflammatory transcription factor, NF-κ B, and upstream signaling molecules, MAPKs, were also significantly attenuated by APEE treatment in LPS-activated RAW 264.7 cells. These results indicate that APEE might be a candidate to be utilized as a promising candidate for the treatment of inflammatory disorders.

• KSBB Journal
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• v.25 no.6
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• pp.507-512
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• 2010

In this study, we investigated the ability of luteolin, a plant derived flavonoid on hepatocarcinoma cell growth using HepG2 cell culture system. We found that luteolin increased the Smac/DIABLO releases, a mitochondrial protein that potentiates apoptosis. Luteolin also induced either transcriptional activity or expression of PPAR-gamma, a target of cancer growth that PPAR-gamma agonist sensitizes to apoptosis in certain cancer types. To find the possible upstream target molecules of PPAR-gamma activated by luteolin treatment, we used compound C, a specific inhibitor of AMP-activated protein kinase. Pre-treatment of Compound C significantly restored the activation or expression of PPAR-gamma stimulated by luteolin. This result indicated that AMPK signaling might be involved in the activation or expression of PPAR-gamma signaling pathway stimulated by luteolin. Moreover, we also found that luteolin inhibited the insulin-stimulated Akt phosphorylation as well as AICAR, a specific AMPK activator. These results propose that luteolin significantly induces cancer cell death through modulating survival signal pathways such as PPAR-gamma and Akt. AMPK signaling pathway may be an upstream regulator for survival signal pathways such as PPAR-gamma and Akt stimulated by luteolin.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.339-346
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• 2000

Using murine immortalized microglial cells (BV-2), we examined the regulation of RANTES production stimulated by lipopolysaccharide (LPS), focusing on the role of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B.$ The result showed that RANTES (regulated upon activation of normal T cell expressed and secreted) was induced at the mRNA and protein levels in a dose- and time-dependent manner in response to LPS. From investigations of second messenger pathways involved in regulating the secretion of RANTES, we found that LPS induced phosphorylation of extracellular signal-regulated kinase (Erk), p38 MAPK and c-Jun-N-terminal kinase (JNK), and activated $(NF)-{\kappa}B.$ To determine whether this MAPK phosphorylation is involved in LPS-stimulated RANTES production, we used specific inhibitors for p38 MAPK and Erk, SB 203580 and PD 98059, respectively. LPS-induced RANTES production was reduced approximately 80% at $25\;{\mu}M$ of SB 203580 treatment. But PD 98059 did not affect RANTES production. Pyrrolidine-dithiocarbamate (PDTC), $(NF)-{\kappa}B$ inhibitor, reduced RANTES secretion. These results suggest that LPS-induced RANTES production in microglial cells (BV-2) is mainly mediated by the coordination of p38 MAPK and $(NF)-{\kappa}B$ cascade.

• Biomedical Science Letters
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• v.20 no.3
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• pp.129-138
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• 2014

In this study, we investigated the effect of water extract from rice bran (RB) on ADP ($20{\mu}M$)-stimulated platelet aggregation. RB dose-dependently inhibited ADP-induced platelet aggregation, and its $IC_{50}$ value was $224.0{\mu}g/mL$, which was increased by adenylate cyclase inhibitor SQ22536 and cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS. RB elevated the phosphorylation of VASP ($Ser^{157}$) which was also inhibited by SQ22536 and Rp-8-Br-cAMPS. It is thought that RB-elevated cAMP contributed to the phosphorylation of VASP ($Ser^{157}$) to inhibit ADP-induced platelet aggregation. Therefore, we demonstrate that RB has an antiplatelet effect via cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and RB may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• International Journal of Industrial Entomology and Biomaterials
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• v.48 no.1
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• pp.13-18
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• 2024

The rice field grasshopper, Oxya chinensis sinuosa (OC), has traditionally been utilized in Korea for various purposes; however, its potential benefits in the context of osteoporosis remain unclear. The results revealed that OC ethanol extract (OCE) significantly inhibited the formation and activity of tartrate-resistant acid phosphatase (TRAP)-positive cells in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated RAW264.7 cells. Furthermore, OCE, at concentrations ranging from 100 to 400 ㎍/mL, demonstrated a dose-dependent reduction in the protein expression of osteoclast-specific markers, including nuclear factor of activated T cell cytoplasmic 1, c-Src, and TRAP, when compared to RANKL stimulation alone. Additionally, OCE significantly inhibited RANKL-induced activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) but not the activation of extracellular signal-regulated kinase. Collectively, these results indicate that OCE suppresses osteoclastogenesis by attenuating the phosphorylation of p38 MAPK and JNK. Consequently, these findings suggest that OCE holds promise for the prevention of osteoporosis.