• Korean Journal of Veterinary Research
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• v.39 no.1
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• pp.55-61
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• 1999

The present experiments were performed to examine the effects of acetylcholine (ACh) and carbachol (CC) on thyroxine ($T_4$) release and any possible relation between inhibition of $T_4$ release and signaling pathway in guinea pig thyroids. The thyroids were incubated in the medium containing the test agents, samples of the medium were assayed for $T_4$ by EIA kits. ACh and CC inhibited the TSH-stimulated $T_4$ release. These inhibition were reversed by atropine, but not by d-tubocurarine. The inhibitory effects of ACh on $T_4$ release were prevented by $M_{1^-}$ and $M_{3^-}$muscarinic antagonists and its inhibition was also slightly reversed by $M_{2^-}$ and $M_{4^-}$muscarinic antagonists. R59022, like ACh and CC, also inhibited the TSH-stimulated $T_4$ release. This inhibition was reversed by protein kinase C inhibitor and $Ca^{2+}$ channel blocker. The present study suggests that cholinergic inhibition of $T_4$ release from thyroids can be induced mainly by activation of the $M_{1^-}$ or $M_{3^-}$ receptors and that it is mediated through the muscarinic receptorstimulated protein kinase C activation.

• Preventive Nutrition and Food Science
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• v.2 no.3
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• pp.236-240
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• 1997

A crude extract of Smphytum officinale L. (comfrey) was for its ability to inhibit he growth of hepatocellular carcinoma cells and expression of the insulin-like growth factor I (IGF-II) gene. The DNA synthesis of hepatocellular carcinoma cell lines, Hep G2, Hep 3B, and PLC/PRF/5 was inhibited by a crude extract of Smphytum officinale in both a time- and a dose-dependent manners. This plant extract also inhibited expression of the IGF-II gene. Since IGF-II exerts a mitogenic effect on Hep G2 cells, these results suggest that the growth inhibition by Symphytum officinale extract is, in part, mediated through the inhibition of IGF-II gene expression.

• Biomedical Science Letters
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• v.11 no.4
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• pp.421-427
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• 2005

To evaluate the diagnostic significance of p16 overexpression in human hepatocellular carcinoma (HCC), we analyzed p16 status and growth inhibitory patterns by p16 overexpression in HCC cell lines having different pRE status. SKHep1 and SNU449 cells show homozygous deletion of p16. The p16 gene in SNU398 cell is inactivated at posttranscription level. Adenovira1-p16 (Ad-p16) infection inhibits the cell growth in Hep3B, SNU398, and SNU449. Failure of growth inhibition in SKHepl results from the low transduction efficiency of adenovirus. The p16-mediated growth inhibition shows G 1 phase arrest in pRE-positive SNU449 but not in pRE-negative Hep3B. These results suggest that therapeutic efficacy of p16 gene might be considered on the transduction efficiency and the toxicity of adenoviral vector. Beside, growth inhibitory effect of p16 could be exerted through either pRE-dependent or -independent pathway.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.87-87
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• 2020

In this study, we investigated the immune-enhancing activity of water extracts from Hydrangea macrophylla subsp. serrata (WE-HML). WE-HML increased cell viability and production of immunomodulators, which contributed to activating phagocytic activity in RAW264.7 cells. Inhibition of JNK and NF-κB reduced the production of immunomodulators by WE-HML. ROS inhibition suppressed the production of immunomodulators, and the activation of JNK and NF-κB signaling by WE-HML. TLR4 inhibition attenuated the production of immunomodulators, and activation of JNK and NF-κB signaling by WE-HML. In the immunosuppressed mouse model, WE-HML increased the spleen index, the levels of the cytokines, the numbers of white blood cells, lymphocytes, and neutrophils. However, WE-HML inhibited LPS-mediated overproduction of pro-inflammatory mediators in RAW264.7 cells, which indicated that WE-HML may have anti-inflammatory activity under excessive inflammatory conditions. Taken together, WE-HML may be considered to have immune-enhancing activity and expected to be used as a potential immune-enhancing agent.

• Animal cells and systems
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• v.13 no.3
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• pp.289-295
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• 2009

Cyclic AMP-mediated signaling pathways regulate a number of cellular functions. In this study, we examined the regulatory role of cAMP signaling pathways in chondrogenesis of chick limb bud mesenchymal cells in vitro. Forskolin, which increases cellular cAMP levels by the activation of adenylate cyclase, enhanced chondrogenic differentiation. Inhibition of PKA with specific inhibitors (H89 or KT5720) blocked pre-cartilage condensation stage, indicating that chondrogenesis is regulated by the increase in cellular cAMP level and subsequent activation of PKA. Downstream signaling pathway of PKA leading to gene expression was investigated by examination of several nuclear transcription factors. Forskolin treatment increased transcription level for a cartilage-specific marker gene Sox9. However, inhibition of PKA with H89 led to restore expression of Sox9, indicating PKA activity was required to regulate the expression of Sox9 in chondrogenesis. In addition, CREB was highly phosphorylated at early stage of mesenchyme culture, and followed by progressive dephosphorylation. CBP and ATF, another CRE related proteins were transiently expressed at the early stage of chondrogenesis with a pattern similar to CREB phosphorylation. Electrophoretic mobility shift assays confirmed that the binding activity of CREB to the CRE is closely correlated to the phosphorylation pattern of CREB. Therefore, cAMP-mediated signal transduction to nuclear events for the induction of genes appeared to be required at the early stage of chick limb bud chondrogenesis.

• BMB Reports
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• v.45 no.8
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• pp.458-463
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• 2012

We investigated the mechanisms involved in KHG26377 regulation of glutamate dehydrogenase (GDH) activity, focusing on the roles of SIRT4 and SIRT3. Intraperitoneal injection of mice with KHG26377 reduced GDH activity with concomitant repression of glucose-induced insulin secretion. Consistent with their known functions, SIRT4 ribosylated GDH and reduced its activity, and SIRT3 deacetylated GDH, increasing its activity. However, KHG26377 did not affect SIRT4-mediated ADP-ribosylation/inhibition or SIRT3-mediated deacetylation/activation of GDH. KHG26377 had no effect on SIRT4 protein levels, and did not alter total GDH, acetylated GDH, or SIRT3 protein levels in pancreatic mitochondrial lysates. These results suggest that the mechanism by which KHG26377 inhibits GDH activity and insulin secretion does not involve ADP-ribosylation of GDH by SIRT4 or deacetylation of GDH by SIRT3.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.495-498
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• 2013

Epidermal growth factor receptor (EGFR) is over-expressed in several human cancers. This would suggest that inhibition of EGFR is a reasonable approach for cancer treatment. In this study we investigated EGFR blocking and its effects on the mediated signaling such as MAPK and STATb in HT29 cells. For this aim we used FITC-labeled EGFR antisense oligonucleotides encapsulated with PAMAM nanoparticles to inhibit EGFR expression. Cellular uptake of antisense was investigated by fluorescence microscopy and flow cytometry analysis. The effect of EGFR antisense on the expression of EGFR in HT29 cells was examined by real time PCR and Western blots, which showed that antisense encapsulated with PAMAM decreased the level of EGFR mRNA and protein. In addition, real time PCR results confirmed that EGFR inhibition had an effective role in the reduction of EGFR dependent downstream genes. In conclusion, EGFR antisense encapsulated with PAMAM nanoparticles down regulated EGFR and EGFR-mediated genes.

• BMB Reports
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• v.35 no.6
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• pp.583-589
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• 2002

The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon $\gamma$ (IFN-$\gamma$). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-$\gamma$-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-$\gamma$ mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.237-242
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• 2011

This study was designed to investigate the effects of glipizide on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Clinically carvedilol and glipizide can be prescribed for treatment of cardiovascular diseases as the complications of diabetes, and then, Carvedilol and glipizide are all substrates of CYP2C9 enzymes. Carvedilol was administered orally or intravenously without or with oral administration of glipizide to rats. The effects of glipizide on cytochrome P450(CYP) 2C9 activity and P-gp activity were also evaluated. Glipizide inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 18 ${\mu}M$. Compared with the control group, the area under the plasma concentration-time curve (AUC) was significantly increased by 33.0%, and the peak concentration ($C_{max}$) was significantly increased by 50.0% in the presence of glipizide after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.13- to 1.33-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of glipizide was increased by 36.8%. After intravenous administration, compared to the control, glipizide could not significantly change the pharmacokinetic parameters of carvedilol. Therefore, the enhanced oral bioavailability of carvedilol may mainly result from inhibition of CYP2C9-mediated metabolism rather than both P-gp-mediated effl ux in the intestinal or in the liver and renal elimination of carvedilol by glipizide.

• BMB Reports
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• v.43 no.9
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• pp.622-628
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• 2010

Dimethyl sulfoxide (DMSO) can be reduced to dimethyl sulfide by MsrA, which stereospecifically catalyzes the reduction of methionine-S-sulfoxide to methionine. Our previous study showed that DMSO can competitively inhibit methionine sulfoxide reduction ability of yeast and mammalian MsrA in both in vitro and in vivo, and also act as a non-competitive inhibitor for mammalian MsrB2, specific for the reduction of methionine-R-sulfoxide, with lower inhibition effects. The present study investigated the effects of DMSO on the physiological antioxidant functions of methionine sulfoxide reductases. DMSO elevated hydrogen peroxide-mediated Saccharomyces cerevisiae cell death, whereas it protected human SK-Hep1 cells against oxidative stress. DMSO reduced the protein-carbonyl content in yeast cells in normal conditions, but markedly increased protein-carbonyl accumulation under oxidative stress. Using Msr deletion mutant yeast cells, we demonstrated the DMSO's selective inhibition of the antioxidant function of MsrA in S. cerevisiae, resulting in an increase in oxidative stress-induced cytotoxicity.