• Title/Summary/Keyword: Signal transduction

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Effect of Calmodulin on Ginseng Saponin-Induced $Ca^{2+}$-Activated $Cl^{-}$ Channel Activation in Xenopus laevis Oocytes

  • Lee Jun-Ho;Jeong Sang-Min;Lee Byung-Hwan;Kim Jong-Hoon;Ko Sung-Ryong;Kim Seung-Hwan;Lee Sang-Mok;Nah Seung-Yeol
    • Archives of Pharmacal Research
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    • v.28 no.4
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    • pp.413-420
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    • 2005
  • We previously demonstrated the ability of ginseng saponins (active ingredients of Panax ginseng) to enhance $Ca^{2+}$-activated $Cl^{-}$ current. The mechanism for this ginseng saponin-induced enhancement was proposed to be the release of $Ca^{2+}$ from $IP_{3}-sensitive$ intracellular stores through the activation of PTX-insensitive $G\alpha_{q/11}$ proteins and PLC pathway. Recent studies have shown that calmodulin (CaM) regulates $IP_{3}$ receptor-mediated $Ca^{2+}$ release in both $Ca^{2+}-dependent$ and -independent manner. In the present study, we have investigated the effects of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current responses in Xenopus oocytes. Intraoocyte injection of CaM inhibited ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement, whereas co-injection of calmidazolium, a CaM antagonist, with CaM blocked CaM action. The inhibitory effect of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement was dose- and time-dependent, with an $IC_{50} of 14.9\pm3.5 {\mu}M$. The inhibitory effect of CaM on saponin's activity was maximal after 6 h of intraoocyte injection of CaM, and after 48 h the activity of saponin recovered to control level. The half-recovery time was calculated to be $16.7\pm4.3 h$. Intraoocyte injection of CaM inhibited $Ca^{2+}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement and also attenuated $IP_{3}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. $Ca^{2+}$/CaM kinase II inhibitor did not inhibit CaM-caused attenuation of ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. These results suggest that CaM regulates ginseng saponin effect on $Ca^{2+}$-activated $Cl^{-}$ current enhancement via $Ca^{2+}$-independent manner.

Screening for Natural Bioactive Compounds Targeting the Intracellular Signal Transduction Pathway: Natural Products Modulating the Expression of the Interleukin-2 gene

  • Hakamatsuka, Takashi
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.60-61
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    • 2003
  • Human Genome Project has recently been completed and the information on nucleotide sequences of our whole genome is now available at the public or commercial data banks. Next goals are to identify the functions of each gene and to elucidate the intracellular signal transduction pathways regulating gene expression. We have established a PCR-based bioassay to search for biologically active compounds that can modulate the expression of genes encoding important proteins. (omitted)

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The roles of ceramide on the cellular signal transduction in RAW 264.7 murine macrophages activated with lipopolysaccharide and interferon-gamma.

  • Park, Sung-Sik;Chun, Young-Jin
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.156.1-156.1
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    • 2003
  • Cerarmide acts as a lipid second messenger in the cellular signal transduction and is involved in mediating a variety of cell functions such as proliferation, differentiation, growth arrest, and apoptosis. In the present study, we have investigated the effect of ceramide on cellular cytotoxity and reactive oxygen species (ROS) to understand the relationship between them. Ceramide treatment significantly increased cell death in RAW 264.7 murine macrophages activated with lipopolysaccharide (LPS) and interferon-g (IFN-g). (omitted)

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m6A in the Signal Transduction Network

  • Jang, Ki-Hong;Heras, Chloe R.;Lee, Gina
    • Molecules and Cells
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    • v.45 no.7
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    • pp.435-443
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    • 2022
  • In response to environmental changes, signaling pathways rewire gene expression programs through transcription factors. Epigenetic modification of the transcribed RNA can be another layer of gene expression regulation. N6-adenosine methylation (m6A) is one of the most common modifications on mRNA. It is a reversible chemical mark catalyzed by the enzymes that deposit and remove methyl groups. m6A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m6A processing. Conversely, m6A can modulate the activity of signal transduction networks via m6A modification of signaling pathway genes or by acting as a ligand for receptors. In this review, we discuss the current understanding of the crosstalk between m6A and signaling pathways and its implication for biological systems.

PHOTOMORPHOGENIC MUTANTS OF TOMATO

  • Kendrick, Richard E.
    • Proceedings of the Botanical Society of Korea Conference
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    • 1994.09a
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    • pp.41-51
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    • 1994
  • Tomato (Lycopersicon esculentum Mill.) has been chosen as a model species for the study of hotomorphogenesis. The aurea (au) and yellow-green-2 (yg-2) mutants which are severely photochrome deficient appear to be phytochrome chromophore mutants. Mutants modified with respect to specific members of the phytochrome gene family: the far-red light-insensitive mutant (fri, for phytochrome A) and the temporarily red light-insensitive mutant (tri, for phytochrome B1) have been identified. Mutants that exhibit an exaggerated phytochrome response are putative transduction-chain mutants affecting an amplification step in phytochrome signal transduction. These mutants are being used to understand the complexities of juvenile anthocyanin in the hypocotyl during seedling de-etiolation.

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The Vomeronasal Organ and Adjacent Glands Express Components of Signaling Cascades Found in Sensory Neurons in the Main Olfactory System

  • Lee, Sang Jin;Mammen, Alex;Kim, Esther J.;Kim, So Yeun;Park, Yun Ju;Park, Mira;Han, Hyung Soo;Bae, Yong-Chul;Ronnett, Gabriele V.;Moon, Cheil
    • Molecules and Cells
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    • v.26 no.5
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    • pp.503-513
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    • 2008
  • The vomeronasal organ (VNO) is a sensory organ that influences social and/or reproductive behavior and, in many cases, the survival of an organism. The VNO is believed to mediate responses to pheromones; however, many mechanisms of signal transduction in the VNO remain elusive. Here, we examined the expression of proteins involved in signal transduction that are found in the main olfactory system in the VNO. The localization of many signaling molecules in the VNO is quite different from those in the main olfactory system, suggesting differences in signal transduction mechanisms between these two chemosensory organs. Various signaling molecules are expressed in distinct areas of VNO sensory epithelium. Interestingly, we found the expressions of groups of these signaling molecules in glandular tissues adjacent to VNO, supporting the physiological significance of these glandular tissues. Our finding of high expression of signaling proteins in glandular tissues suggests that neurohumoral factors influence glandular tissues to modulate signaling cascades that in turn alter the responses of the VNO to hormonal status.

Serum miR-19a Predicts Resistance to FOLFOX Chemotherapy in Advanced Colorectal Cancer Cases

  • Chen, Qi;Xia, Hong-Wei;Ge, Xiao-Jun;Zhang, Yu-Chen;Tang, Qiu-Lin;Bi, Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7421-7426
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    • 2013
  • Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. Methods: To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative real-time PCR. Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.

Comparative study of Photobacterium damselae subsp. damselae and Vibrios on pathogenicity in vitro (In vitro에서 Photobacterium damselae subsp. damselae와 Vibrio 속 세균의 병원성 비교)

  • Kwon, Mun-Gyeong;Kim, Myoung-Sug;Cho, Byoung-Youl;Kim, Jin-Woo;Park, Soo-Il
    • Journal of fish pathology
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    • v.20 no.1
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    • pp.71-81
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    • 2007
  • Photobacterium damselae subsp. damselae and 4 Vibrio spp.(V. anguillarum, V. splendidus, V. harveyi and V. ordalii) were isolated from the diseased olive flounders, Paralichthys olivaceus. The isolates were tested on the pathogenicity in vitro. The properties of extracellular products(ECPs) were investigated with enzymatic activities, hemolytic activities toward the sheep and olive flounder erythrocytes, and cytotoxicity activities on the cell-line. And potential signal transduction pathways of the bacterial internalization were detected by using signal transduction inhibitors. P. damselae was high in phospholipase activity, hemolytic activity to olive flounder erythrocytes and cytotoxicity activity. And P. damselae had diversified internalizing pathways as compared to isolated vibrios. Therefore, these activities may be related with pathogenicity of P. damselae.