• YAKHAK HOEJI
• /
• v.45 no.3
• /
• pp.287-292
• /
• 2001

To investigate whether phospholipase $A_2$pathway is involved in histamine release of rat peritoneal mast cells, we measured histamine release in the presence of various enzyme inhibitors involved in eicosanoid pathway, such as phospholipase $A_2$, cyclooxygenase and lipoxygenase. Phospholipase $A_2$inhibitors, manoalide and OPC, significantly inhibited histamine release induced by 100 $\mu$M ATP and 1$\mu$g/ml compound 48/80. Cyclooxygenase inhibitors, ibuprofen and indomethacin, significantly inhibited ATP-induced histamine release and lipoxygenase inhibitors, baicalein and caffeic acid, also significantly inhibited. To investigate the involvement of protein kinase in ATP- and compound 48/80-induced histamine release, we observed effects of protein kinase inhibitors on histamine release. Bisindolmaleimide (protein kinase C antagonist) dose-dependently inhibited both ATP and compound 48/80-induced histamine release. Tyrosine kinase inhibitors (methyl 2,5-dihydroxy cinnamate and genistein) dose-dependently inhibited ATP and compound 48/80-induced histamine release. Protein kinase C and tyrosine kinase seem to be involved in histamine release induced by ATP and compound 48/80. These results suggest that phospholipase $A_2$pathway as well as protein kinase C and tyrosine kinase are involved in histamine release of rat peritoneal mast cells by ATP and compound 48/80.

• Nuclear Engineering and Technology
• /
• v.53 no.9
• /
• pp.2878-2887
• /
• 2021

As the amount of fission product released from ISLOCA was overestimated because of conservative assumptions in the past, several studies have been recently conducted to evaluate the actual release amount. Among several pathways for the ISLOCA, most studies were focused on the pathway with the highest possibility. However, different ISLOCA pathways may have different fission product release characteristics. In this study, fission product behavior was analyzed for various pathways at the Westinghouse two-loop plant using MELCOR. Four pathways are considered: the pipes from a cold leg, from a downcomer, from a hot leg to the outlet of RHR heat exchanger, and the pipe from the hot leg to the inlet of RHR pump (Pathway 1-4). According to the analysis results, cladding fails at around 2.5 h in Pathways 1 and 2, and on the other hand, about 3.3 h in Pathways 3 and 4 because the ISLOCA pathways affect the safety injection flow path. While the release amount of cesium and iodine ranges between 20 and 26% in Pathways 1 to 3, Pathway 4 allows only 5% to the environment because the break location is submerged. Also, as more than 90% of cesium released to the environment passes through the personnel door, reinforcing the pressure capacity of the doors would be a significant factor in the accident management of the ISLOCA.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1996.04a
• /
• pp.219-219
• /
• 1996

Mucin release from hamster tracheal surface epithelial(HTSE) cells can be stimulated by extracellular ATP via activation of P$_2$ purinoceptors located on the cell surface which appears to be coupled to phospholipase C via G proteins. However, our preliminary data indicate that the ATP-induced mucin release involves, in part, activation of PKC, but not an increase in the intracellular Ca++ level, suggesting the presence of another pathway which is separate from the PLC-PKC pathway, In this study, we intended to confirm the previous observation and subsequently identify an additional mechanism. Confluent HTSE cells were metabolically labeled with either $^3$H-glucosamine or $^3$H-arachidonic acid(AA), and release of either $^3$H-mucin or $^3$H-AA was quantified following various treatments. $^3$H-mucin was assayed using the sepharose CL-4B gel-filtration method, whereas $^3$H-AA liberation was measured by counting $^3$H-radioactivity in the chase medium. We found that: (1)Desensitization of PKC by pretreatment with PMA completely abolished the mucin releasing effect of PMA but partially inhibited the ATP-induced mucin release; (2) ATP increases release of $^3$H-AA in a dose-dependent fashion; (3) mepacrine, an inhibitor of PLA$_2$, attenuates ATP-induced mucin release in a dose-dependent fashion. These results confirm our previous notion that the PLC-PKC pathway is responsible, in part, for ATP-induced mucin release. Furthermore, activation of PLA$_2$ appears to be an additional pathway which is involved in ATP-induced mucin release.

• Nuclear Engineering and Technology
• /
• v.26 no.1
• /
• pp.78-89
• /
• 1994

The radionuclide release rates from the engineered barrier composed of concrete structure and clay-based backfill in a low and intermediate level waste repository were assessed. Four types of release pathway were considered, and the contribution of each pathway to the total release were analyzed. To quantify the effect of uncertainties of input parameter values on the assessment of radionuclide release rates, the Latin Hypercube sampling method was used, and the resulting release rate distribution were determined through a goodness-of-fit test. Finally, the ranges of maxi-mum release rates ore estimated statistically with a confidence level of 95%.

• BMB Reports
• /
• v.38 no.5
• /
• pp.619-623
• /
• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.21
• /
• pp.9153-9157
• /
• 2014

Background: Capparis spinosa L., a Uygur medicine, had been shown to have anti-tumor activity in our early experiments with an N-butanol extract (CSBE) as its active fraction. However, the mechanisms responsible for its effects are not clearly understood. Here, we report that treatment of SGC-7901 cells with CSBE resulted in dose-dependent reduction of cell viability and induction of apoptosis. Materials and Methods: To observe the inhibitory and killing effects of CSBE on SGC-7901, the SRB method was adopted, apoptosis being observed by electron microscopy. To clarify the mechanisms of apoptosis, Western blot and enzyme-labeled methods were used to examine the release of cytochrome c (Cyt c) and the activation of the caspase cascade. Results: By electron microscopy, apoptotic morphologic changes were detectable after CSBE administration. In this study, it was also demonstrated that CSBE induced apoptosis in SGC-7901 cells by inhibiting mPTP open, mitochondrial cytochrome c release, caspase-9 and caspase-3 activation. Conclusions: The findings indicated that CSBE induces aap optosis through mitochondrial pathway.

• Journal of Dental Rehabilitation and Applied Science
• /
• v.36 no.3
• /
• pp.145-157
• /
• 2020

Purpose: This study was to determine the possible effects of trichloroacetic acid (TCA) and epidermal growth factor (EGF) through cell survival genes of the PI3K-AKT signaling pathway when applying an hydrophobically modified glycol chitosan (HGC)-based nanocontrolled release system to human gingival fibroblasts in oral soft tissue regeneration. Materials and Methods: An HGC-based nano-controlled release system was produced, followed by the loading of TCA and EGF. The group was divided into control (CON), TCA-loaded nano-controlled release system (EXP1), and the TCA- and EGF- individually loaded nano-controlled release system (EXP2). A total for 29 genes related to the PI3K-AKT signaling pathway were analyzed after 48h of culture in human gingival fibroblasts. Real-time PCR, 1- way ANOVA and multiple regression analysis were performed. Results: Cell survival genes were significantly upregulated in EXP1 and EXP2. From multiple regression analysis, ITGB1 was determined to be the most influential factor for AKT1 expression. Conclusion: The application of TCA and EGF through the HGC-based nano-controlled release system can up-regulate the cell survival pathway.

• YAKHAK HOEJI
• /
• v.51 no.1
• /
• pp.63-67
• /
• 2007

To investigate the relation between extracellular Ca$^{2+}$ and histamine release, we observed agonist-induced histamine release from RBL 2H3 mast cells in the presence or absence of extracellular Ca$^{2+}$ concentration. Histamine release induced by melittin and thapsigargin were greater in the presence of extracellular Ca$^{2+}$ than in the absence of extracellular Ca$^{2+}$. Econazole-induced histamine release had nothing to do with extracellular Ca$^{2+}$, whereas arachidonic acid-induced histamine release increased in the absence of extracellular Ca$^{2+}$. Calmodulin antagonists did not affect melittin-induced histamine release but they may potentiate arachidonic acid-induced histamine release. These data suggest that arachidonic acid-induced histamine release may be mediated via Ca$^{2+}$-independent pathway and may be potentiated by the block of Ca$^{2+}$-dependent pathway.

• Journal of Periodontal and Implant Science
• /
• v.35 no.2
• /
• pp.427-436
• /
• 2005

Objective: MMP-8 is a neutrophil enzyme and its level increases in some inflammatory diseases, including periodontal disease. We knew that the lipopolysaccharide of E.coli(E-LPS) induced MMP-8 release from human neutrophils. E-LPS is known to induce the production and release of inflammatory cytokines through CD14, Toll-like receptor(TLR). In the present study, we investigated whether MMP-8 release by E-LPS is induced via CD14-TLR pathway and the cellular mechanism of MMP-8 release in human neutrophils. Material and methods: Human neutrophils were isolated from the peripheral blood of healthy donors and pre-incubated in medium containing antibodies against CD14, anti-TLR2 and anti-TLR4 or several inhibitors of microtubules and microfilaments and then incubated with E-LPS. The cells were treated TPCK and E-LPS simultaneously. The MMP-8amount in the culture medium was determined using ELISA. Results: E-LPS increased MMP-8release from neutrophils and its induction was inhibited by anti-CD14 and anti-TLR4 but not by anti-TLR2 antibodies. The inhibitors of microtubule and microfilament polymerization significantly decreased E-LPS-induced MMP-8release. TPCK inhibited E-LPS-induced MMP-8 release. Conclusion: These results suggest that MMP-8 release is induced by E-LPS via the CD14-TLR4 signal pathway in human neutrophils and may be depedent on microtubule and microfilament systems and $NF-{\kappa}B$ pathway.

• IMMUNE NETWORK
• /
• v.12 no.4
• /
• pp.148-154
• /
• 2012

Previously, we have reported that high mobility group box 1 (HMGB1), a proinflammatory mediator in sepsis, is released via the IFN-${\beta}$-mediated JAK/STAT pathway. However, detailed mechanisms are still unclear. In this study, we dissected upstream signaling pathways of HMGB1 release using various molecular biology methods. Here, we found that calcium/calmodulin-dependent protein kinase (CaM kinase, CaMK) is involved in HMGB1 release by regulating IFN-${\beta}$ production. CaMK inhibitor, STO609, treatment inhibits LPS-induced IFN-${\beta}$ production, which is correlated with the phosphorylation of interferon regulatory factor 3 (IRF3). Additionally, we show that CaMK-I plays a major role in IFN-${\beta}$ production although other CaMK members also seem to contribute to this event. Furthermore, the CaMK inhibitor treatment reduced IFN-${\beta}$ production in a murine endotoxemia. Our results suggest CaMKs contribute to HMGB1 release by enhancing IFN-${\beta}$ production in sepsis.