• Title/Summary/Keyword: Signaling crosstalk

Search Result 54, Processing Time 0.021 seconds

Rheumatoid Fibroblast-like Synoviocytes Downregulate Foxp3 Expression by Regulatory T Cells Via GITRL/GITR Interaction

  • Kim, Sung Hoon;Youn, Jeehee
    • IMMUNE NETWORK
    • /
    • v.12 no.5
    • /
    • pp.217-221
    • /
    • 2012
  • Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.

A Molecular Model for Light Signal Perception and Interdomain Crosstalk in Phytochrome Photoreceptors

  • Song, Pill-Soon;Park, Chung-Mo
    • Journal of Photoscience
    • /
    • v.7 no.3
    • /
    • pp.79-86
    • /
    • 2000
  • Phytochromes are red and far-red light absorbing photoreceptors for photomorphogenesis in plants. The red/far wavelength reversible biliproteins are made up of two structural domains. The light-perceiving function of the photoreceptor resides in the N-terminal domain, whereas the signal transducing regulatory function is located within the C-terminal domain. The characteristic role of the phytochromes as phtosensory molecular switches is derived from the phototransformation between two distinct spectral forms, the red light absorbing Pr and the far-red light absorbing Pfr forms. The photoinduced Pr Pfr phototransformation accompanies subtle conformational changes throughout the phytochrome molecule. The conformational signals are subsequently transmitted to the C-terminal domain through various inter-domain crosstalks and induce the interaction of the activated C-terminal domain with phytochrome interacting factors. Thus the inter-domain crosstalks play critical roles in the photoactivation of the phytochromes. Posttranslational modifications, such as the phosphorylation of Ser-598, are also involved in this process through conformational changes and by modulating inter-domain signaling.

  • PDF

Crosstalk of Zn in Combination with Other Fertilizers Underpins Interactive Effects and Induces Resistance in Tomato Plant against Early Blight Disease

  • Awan, Zoia Arshad;Shoaib, Amna;Khan, Kashif Ali
    • The Plant Pathology Journal
    • /
    • v.35 no.4
    • /
    • pp.330-340
    • /
    • 2019
  • The present study was undertaken to evaluate the integrated effect of zinc (Zn) with other nutrients in managing early blight (EB) disease in tomato. A pot experiment was carried out with basal application of the recommended level of macronutrients [nitrogen, phosphorus and potassium (NPK)] and micronutrients [magnesium (Mg) and boron (B)] in bilateral combination with Zn (2.5 and 5.0 mg/kg) in a completely randomized deigned in replicates. Results revealed that interactive effect of Zn with Mg or B was often futile and in some cases synergistic. Zn with NPK yield synergistic outcome, therefore EB disease was managed significantly (disease incidence: 25% and percent severity index: 13%), which resulted in an efficient signaling network that reciprocally controls nutrient acquisition and uses with improved growth and development in a tomato plant. Thus, crosstalk and convergence of mechanisms in metabolic pathways resulted in induction of resistance in tomato plant against a pathogen which significantly improved photosynthetic pigment, total phenolics, total protein content and defense-related enzymes [superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL)]. The tremendous increase in total phenolics and PAL activity suggesting their additive effect on salicylic acid which may help the plant to systemically induce resistance against pathogen attack. It was concluded that interactive effect of Zn (5.0 mg/kg) with NPK significantly managed EB disease and showed positive effect on growth, physiological and biochemical attributes therefor use of Zn + NPK is simple and credible efforts to combat Alternaria stress in tomato plants.

Coordinated alteration of mRNA-microRNA transcriptomes associated with exosomes and fatty acid metabolism in adipose tissue and skeletal muscle in grazing cattle

  • Muroya, Susumu;Ogasawara, Hideki;Nohara, Kana;Oe, Mika;Ojima, Koichi;Hojito, Masayuki
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.33 no.11
    • /
    • pp.1824-1836
    • /
    • 2020
  • Objective: On the hypothesis that grazing of cattle prompts organs to secrete or internalize circulating microRNAs (c-miRNAs) in parallel with changes in energy metabolism, we aimed to clarify biological events in adipose, skeletal muscle, and liver tissues in grazing Japanese Shorthorn (JSH) steers by a transcriptomic approach. Methods: The subcutaneous fat (SCF), biceps femoris muscle (BFM), and liver in JSH steers after three months of grazing or housing were analyzed using microarray and quantitative polymerase chain reaction (qPCR), followed by gene ontology (GO) and functional annotation analyses. Results: The results of transcriptomics indicated that SCF was highly responsive to grazing compared to BFM and liver tissues. The 'Exosome', 'Carbohydrate metabolism' and 'Lipid metabolism' were extracted as the relevant GO terms in SCF and BFM, and/or liver from the >1.5-fold-altered mRNAs in grazing steers. The qPCR analyses showed a trend of upregulated gene expression related to exosome secretion and internalization (charged multivesicular body protein 4A, vacuolar protein sorting-associated protein 4B, vesicle associated membrane protein 7, caveolin 1) in the BFM and SCF, as well as upregulation of lipolysis-associated mRNAs (carnitine palmitoyltransferase 1A, hormone-sensitive lipase, perilipin 1, adipose triglyceride lipase, fatty acid binding protein 4) and most of the microRNAs (miRNAs) in SCF. Moreover, gene expression related to fatty acid uptake and inter-organ signaling (solute carrier family 27 member 4 and angiopoietin-like 4) was upregulated in BFM, suggesting activation of SCF-BFM organ crosstalk for energy metabolism. Meanwhile, expression of plasma exosomal miR-16a, miR-19b, miR-21-5p, and miR-142-5p was reduced. According to bioinformatic analyses, the c-miRNA target genes are associated with the terms 'Endosome', 'Caveola', 'Endocytosis', 'Carbohydrate metabolism', and with pathways related to environmental information processing and the endocrine system. Conclusion: Exosome and fatty acid metabolism-related gene expression was altered in SCF of grazing cattle, which could be regulated by miRNA such as miR-142-5p. These changes occurred coordinately in both the SCF and BFM, suggesting involvement of exosome in the SCF-BFM organ crosstalk to modulate energy metabolism.

Regulation of Adenosine-activated GIRK Channels by Gq-coupled Receptors in Mouse Atrial Myocytes

  • Cho, Ha-Na
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.14 no.3
    • /
    • pp.145-150
    • /
    • 2010
  • Adenosine (Ado) is an important mediator of the endogenous defense against ischemia-induced injury in the heart. The action of Ado is mediated by activation of G protein-gated inwardly rectifying $K^+$ (GIRK) channels. In turn, GIRK channels are inhibited by reducing phosphatidylinositol 4,5-bisphosphate ($PIP_2$) through Gq protein-coupled receptors (GqPCRs). We previously found that GIRK channels activated by acetylcholine, a muscarinic M2 acetylcholine receptor agonist, are inhibited by GqPCRs in a receptor-specific manner. However, it is not known whether GIRK channels activated by Ado signaling are also regulated by GqPCRs. Presently, this was investigated in mouse atrial myocytes using the patch clamp technique. GIRK channels were activated by $100\;{\mu}M$ Ado. When Ado was repetitively applied at intervals of 5~6 min, the amplitude of second Ado-activated GIRK currents ($I_{K(Ado)}$) was $88.3{\pm}3.7%$ of the first $I_{K(Ado)}$ in the control. Pretreatment of atrial myocytes with phenylephrine, endothelin-1, or bradykinin prior to a second application of Ado reduced the amplitude of the second $I_{K(Ado)}$ to $25.5{\pm}11.6%$, $30.5{\pm}5.6%$, and $96.0{\pm}2.7%$, respectively. The potency of $I_{K(Ado)}$ inhibition by GqPCRs was different with that observed in acetylcholine-activated GIRK currents ($I_{K(ACh)}$) (endothelin-1>phenylephrine>bradykinin). $I_{K(Ado)}$ was almost completely inhibited by $500\;{\mu}M$ of the $PIP_2$ scavenger neomycin, suggesting low $PIP_2$ affinity of $I_{K(Ado)}$. Taken together, these results suggest that the crosstalk between GqPCRs and the Ado-induced signaling pathway is receptor-specific. The differential change in $PIP_2$ affinity of GIRK channels activated by Ado and ACh may underlie, at least in part, their differential responses to GqPCR agonists.

Altered Cultivar Resistance of Kimchi Cabbage Seedlings Mediated by Salicylic Acid, Jasmonic Acid and Ethylene

  • Lee, Young Hee;Kim, Sang Hee;Yun, Byung-Wook;Hong, Jeum Kyu
    • The Plant Pathology Journal
    • /
    • v.30 no.3
    • /
    • pp.323-329
    • /
    • 2014
  • Two cultivars Buram-3-ho (susceptible) and CR-Hagwang (moderate resistant) of kimchi cabbage seedlings showed differential defense responses to anthracnose (Colletotrichum higginsianum), black spot (Alternaria brassicicola) and black rot (Xanthomonas campestris pv. campestris, Xcc) diseases in our previous study. Defense-related hormones salicylic acid (SA), jasmonic acid (JA) and ethylene led to different transcriptional regulation of pathogenesis-related (PR) gene expression in both cultivars. In this study, exogenous application of SA suppressed basal defenses to C. higginsianum in the 1st leaves of the susceptible cultivar and cultivar resistance of the 2nd leaves of the resistant cultivar. SA also enhanced susceptibility of the susceptible cultivar to A. brassicicola. By contrast, SA elevated disease resistance to Xcc in the resistant cultivar, but not in the susceptible cultivar. Methyl jasmonate (MJ) treatment did not affect the disease resistance to C. higginsianum and Xcc in either cultivar, but it compromised the disease resistance to A. brassicicola in the resistant cultivar. Treatment with 1-aminocyclopropane-1-carboxylic acid (ACC) ethylene precursor did not change resistance of the either cultivar to C. higginsianum and Xcc. Effect of ACC pretreatment on the resistance to A. brassicicola was not distinguished between susceptible and resistant cultivars, because cultivar resistance of the resistant cultivar was lost by prolonged moist dark conditions. Taken together, exogenously applied SA, JA and ethylene altered defense signaling crosstalk to three diseases of anthracnose, black spot and black rot in a cultivar-dependent manner.

High Speed Low Power Decision-Feedback Equalizer Techniques (고속 저전력 결정-피드백 이퀄라이저 기술 동향)

  • Min, Woong-Ki;Kong, Bai-Sun
    • Journal of IKEEE
    • /
    • v.20 no.3
    • /
    • pp.285-290
    • /
    • 2016
  • Inter-symbol interference (ISI) due to channel bandwidth limitation constrains the maximum data rate in high speed I/O. Decision feedback equalizer (DFE) is known as the most popular technique for removing ISI. To ensure fast data transmission, not only removing ISI but also raising maximum operating frequency of the circuit itself by relaxing feedback delay margin is important. For single-ended signaling, DFE should cancel out both ISI and high frequency noises. Low-power operation is as important as fast operation because required DFE elements increase as the data rate goes up. This paper surveys recent techniques for fast DFE by removing ISI and high frequency noises, and low power DFE and discusses about their merits and limitations.

How Extracellular Reactive Oxygen Species Reach Their Intracellular Targets in Plants

  • Jinsu Lee;Minsoo Han;Yesol Shin;Jung-Min Lee;Geon Heo;Yuree Lee
    • Molecules and Cells
    • /
    • v.46 no.6
    • /
    • pp.329-336
    • /
    • 2023
  • Reactive oxygen species (ROS) serve as secondary messengers that regulate various developmental and signal transduction processes, with ROS primarily generated by NADPH OXIDASEs (referred to as RESPIRATORY BURST OXIDASE HOMOLOGs [RBOHs] in plants). However, the types and locations of ROS produced by RBOHs are different from those expected to mediate intracellular signaling. RBOHs produce O2•- rather than H2O2 which is relatively long-lived and able to diffuse through membranes, and this production occurs outside the cell instead of in the cytoplasm, where signaling cascades occur. A widely accepted model explaining this discrepancy proposes that RBOH-produced extracellular O2•- is converted to H2O2 by superoxide dismutase and then imported by aquaporins to reach its cytoplasmic targets. However, this model does not explain how the specificity of ROS targeting is ensured while minimizing unnecessary damage during the bulk translocation of extracellular ROS (eROS). An increasing number of studies have provided clues about eROS action mechanisms, revealing various mechanisms for eROS perception in the apoplast, crosstalk between eROS and reactive nitrogen species, and the contribution of intracellular organelles to cytoplasmic ROS bursts. In this review, we summarize these recent advances, highlight the mechanisms underlying eROS action, and provide an overview of the routes by which eROS-induced changes reach the intracellular space.

Regulator of G-Protein Signaling 4 (RGS4) Controls Morphine Reward by Glutamate Receptor Activation in the Nucleus Accumbens of Mouse Brain

  • Kim, Juhwan;Lee, Sueun;Kang, Sohi;Jeon, Tae-Il;Kang, Man-Jong;Lee, Tae-Hoon;Kim, Yong Sik;Kim, Key-Sun;Im, Heh-In;Moon, Changjong
    • Molecules and Cells
    • /
    • v.41 no.5
    • /
    • pp.454-464
    • /
    • 2018
  • Crosstalk between G-protein signaling and glutamatergic transmission within the brain reward circuits is critical for long-term emotional effects (depression and anxiety), cravings, and negative withdrawal symptoms associated with opioid addiction. A previous study showed that Regulator of G-protein signaling 4 (RGS4) may be implicated in opiate action in the nucleus accumbens (NAc). However, the mechanism of the NAc-specific RGS4 actions that induce the behavioral responses to opiates remains largely unknown. The present study used a short hairpin RNA (shRNA)-mediated knock-down of RGS4 in the NAc of the mouse brain to investigate the relationship between the activation of ionotropic glutamate receptors and RGS4 in the NAc during morphine reward. Additionally, the shRNA-mediated RGS4 knock-down was implemented in NAc/striatal primary-cultured neurons to investigate the role that striatal neurons have in the morphine-induced activation of ionotropic glutamate receptors. The results of this study show that the NAc-specific knock-down of RGS4 significantly increased the behaviors associated with morphine and did so by phosphorylation of the GluR1 (Ser831) and NR2A (Tyr1325) glutamate receptors in the NAc. Furthermore, the knock-down of RGS4 enhanced the phosphorylation of the GluR1 and NR2A glutamate receptors in the primary NAc/striatal neurons during spontaneous morphine withdrawal. These findings show a novel molecular mechanism of RGS4 in glutamatergic transmission that underlies the negative symptoms associated with morphine administration.

A Performance Analysis for Interconnections of 3D ICs with Frequency-Dependent TSV Model in S-parameter

  • Han, Ki Jin;Lim, Younghyun;Kim, Youngmin
    • JSTS:Journal of Semiconductor Technology and Science
    • /
    • v.14 no.5
    • /
    • pp.649-657
    • /
    • 2014
  • In this study, the effects of the frequency-dependent characteristics of through-silicon vias (TSVs) on the performance of 3D ICs are examined by evaluating a typical interconnection structure, which is composed of 32-nm CMOS inverter drivers and receivers connected through TSVs. The frequency-domain model of TSVs is extracted in S-parameter from a 3D electromagnetic (EM) method, where the dimensional variation effect of TSVs can be accurately considered for a comprehensive parameter sweep simulation. A parametric analysis shows that the propagation delay increases with the diameter and height of the TSVs but decreases with the pitch and liner thickness. We also investigate the crosstalk effect between TSVs by testing different signaling conditions. From the simulations, the worst signal integrity is observed when the signal experiences a simultaneously coupled transition in the opposite direction from the aggressor lines. Simulation results for nine-TSV bundles having regular and staggered patterns reveal that the proposed method can characterize TSV-based 3D interconnections of any dimensions and patterns.