• Title/Summary/Keyword: Intracellular signaling

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3D Structure Prediction of Human 5-Hydroxytryptamine Receptor 7 (5-HT7R)

  • Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.11 no.2
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    • pp.87-92
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    • 2018
  • 5-Hydroxytryptamine receptor 7 ($5-HT_7R$) is one of G-Protein coupled receptors, which is found to be involved in the pathophysiology of various neurological disorders including depression, sleep disorders, memory deficiency and neuropathic pain. After activation of $5-HT_7R$ by serotonin, it activates the production of the intracellular signaling molecule cyclic AMP. The availability of 3D structure of the receptor would enhance the development of new drugs. Hence, in the present study, homology modelling of human 5-hydroxytryptamine receptor 7 ($5-HT_7R$) was performed using comparative modelling (Easy Modeller) and threading (I-TASSER) approaches. The generated models were validated using Ramachandran plot and ERRAT plot and the best models were selected based on the validation results. The 3D model developed here could be useful for identifying crucial residues and further docking study.

Protective Effects of Ginseng Coffee against Hydrogen Peroxide-induced Oxidative Damage in L6 Muscle Cells

  • Lee, Yeon-Mi;Kim, Kyung-Tack;Bae, Hye-Min;Lee, Young-Chul;Choi, Sang-Yoon
    • Journal of Ginseng Research
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    • v.34 no.2
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    • pp.145-149
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    • 2010
  • This study investigated the antioxidant effects of ginseng coffee in L6 muscle cells. Ginseng coffee was prepared by coating and digesting coffee beans with ginseng concentrate. The ginseng coffee water extract potently protected against hydrogen peroxide-induced L6 cell death and adenosine triphosphate reduction in a dose-dependent manner; in fact, these cytoprotective effects were significantly greater than those of normal coffee. However, ginseng coffee did not exhibit significant radical scavenging or catalase-like activity. These results suggest that ginseng coffee might act as a cytoprotective agent in muscles, but that the protective effects are not due to a direct radical-reduction property but rather to another intracellular signaling factor.

Psychiatric Implication of Synaptic Adhesion Molecules and Scaffold Proteins (시냅스 접착 단백질과 구조 단백질의 정신과적 의의)

  • Oh, Daeyoung
    • Korean Journal of Biological Psychiatry
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    • v.17 no.3
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    • pp.119-126
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    • 2010
  • Synaptic adhesion molecules mediate synapse formation, maturation and maintenance. These proteins are localized at synaptic sites in neuronal axons and dendrites. These proteins function as a bridge of synaptic cleft via interaction with another synaptic adhesion molecules in the opposite side. They can interact with scaffold proteins via intracellular domain and recruit many synaptic proteins, signaling proteins and synaptic vesicles. Scaffold proteins function as a platform in dendritic spines or axonal terminals. Recently, many genetic studies have revealed that synaptic adhesion molecules and scaffold proteins are important in neurodevelopmental disorders, psychotic disorders, mood disorders and anxiety disorders. In this review, fundamental mechanisms of synapse formation and maturation related with synaptic adhesion molecules and scaffold proteins are introduced and their psychiatric implications addressed.

Nerve growth factor-induced neurite outgrowth is potentiated by stabilization of TrkA receptors

  • Song, Eun-Joo;Yoo, Young-Sook
    • BMB Reports
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    • v.44 no.3
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    • pp.182-186
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    • 2011
  • Exogenous stimuli such as nerve growth factor (NGF) exert their effects on neurite outgrowth via Trk neurotrophin receptors. TrkA receptors are known to be ubiquitinated via proteasome inhibition in the presence of NGF. However, the effect of proteasome inhibition on neurite outgrowth has not been studied extensively. To clarify these issues, we investigated signaling events in PC12 cells treated with NGF and the proteasome inhibitor MG132. We found that MG132 facilitated NGF-induced neurite outgrowth and potentiated the phosphorylation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways and TrkA receptors. MG132 stimulated internalization of surface TrkA receptor and stabilized intracellular TrkA receptor, and the $Ub^{K63}$ chain was found to be essential for stability. These results indicate that the ubiquitin-proteasome system potentiated neurite formation by regulating the stability of TrkA receptors.

Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes

  • Keum, Young-Sam
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.144-151
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    • 2012
  • The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described.

Posttranslational and epigenetic regulation of the CLOCK/BMAL1 complex in the mammalian

  • Lee, Yool;Kim, Kyung-Jin
    • Animal cells and systems
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    • v.16 no.1
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    • pp.1-10
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    • 2012
  • Most living organisms synchronize their physiological and behavioral activities with the daily changes in the environment using intrinsic time-keeping systems called circadian clocks. In mammals, the key molecular features of the internal clock are transcription- and translational-based negative feedback loops, in which clock-specific transcription factors activate the periodic expression of their own repressors, thereby generating the circadian rhythms. CLOCK and BMAL1, the basic helix-loop-helix (bHLH)/PAS transcription factors, constitute the positive limb of the molecular clock oscillator. Recent investigations have shown that various levels of posttranslational regulation work in concert with CLOCK/BMAL1 in mediating circadian and cellular stimuli to control and reset the circadian rhythmicity. Here we review how the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways.

Skeletal Development - Wnts Are in Control

  • Hartmann, Christine
    • Molecules and Cells
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    • v.24 no.2
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    • pp.177-184
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    • 2007
  • Approximately 200 individual skeletal elements, which differ in shape and size, are the building blocks of the vertebrate skeleton. Various features of the individual skeletal elements, such as their location, shape, growth and differentiation rate, are being determined during embryonic development. A few skeletal elements, such as the lateral halves of the clavicle and parts of the skull are formed by a process called intramembranous ossification, whereby mesenchymal cells differentiate directly into osteoblasts, while the majority of skeletal elements are formed via endochondral ossification. The latter process starts with the formation of a cartilaginous template, which eventually is being replaced by bone. This requires co-regulation of differentiation of the cell-types specific for cartilage and bone, chondrocytes and osteoblasts, respectively. In recent years it has been demonstrated that Wnt family members and their respective intracellular pathways, such as non-canonical and the canonical $Wnt/{\beta}$-catenin pathway, play important and diverse roles during different steps of vertebrate skeletal development. Based on the recent discoveries modulation of the canonical Wnt-signaling pathway could be an interesting approach to direct stem cells into certain skeletal lineages.

$Na^+/Ca^{2+}$ exchanger (NCX)-2, a temporal factor in regulation of synaptic plasticity and cognition

  • Shin, Hee-Sup
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.21-21
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    • 2003
  • The role of a postsynaptic rise of [C $a^{2+}$]$_{i}$ in the induction of LTP and LTD has been well established. Both the levels and the duration of elevated [C $a^{2+}$]$_{i}$ are important in synaptic plasticity. LTP and LTD could be selectively induced according to intracellular $Ca^{2+}$ concentration. Although the specificity of $Ca^{2+}$ signaling can be achieved not only by amplitude but also by the frequency and duration of the calcium transient, the effects of changing amplitudes of $Ca^{2+}$ transients on synaptic plasticity have been extensively documented, but not so the effects of temporal changes.changes..

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Inhibitory effects of Thalictrum rochebrunianum var. grandisepalum on tyrosinase in IBMX-induced B16F10 melanoma cells

  • Jang, Tae-Won;Choi, Ji-Soo;Mun, Jeong-Yun;Im, Jong-Yun;Nam, Su-Hwan;Kim, Do-Wan;Lee, Seung-Hyun;Park, Jae-Ho
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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    • pp.116-116
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    • 2019
  • Thalictrum rochebrunianum var. grandisepalum (TRG) is a Korean endemic plant, and it is widely used for edible, medicinal, landscape materials. In this study, we examined the protein and mRNA expression levels of MITF, tyrosinase, TRP-1 and TRP-2 by TRG extract (TRGE) in IBMX-treated melanocytes to evaluate the possibility of using TRG as a whitening material. IBMX were reported as melanin synthesis enhancers. It could increase intracellular melanin synthesis by activation of the microphthalmia-associated transcription factor (MITF) signaling pathway. TRGE did not show cytotoxicity at concentrations below $100{\mu}g/ml$ in B16F10 cells. TREG dose-dependently inhibited protein and mRNA levels of MITF, tyrosinase, TRP-1 and TRP-2. Therefore, we suggest that TRGE is an important natural resource for cosmetic raw materials for whitening function.

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