• 제목/요약/키워드: membrane targeting

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Autoimmune encephalitis and epilepsy: evolving definition and clinical spectrum

  • Seo, Joo Hee;Lee, Yun-Jin;Lee, Ki Hyeong;Gireesh, Elakkat;Skinner, Holly;Westerveld, Michael
    • Clinical and Experimental Pediatrics
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    • 제63권8호
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    • pp.291-300
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    • 2020
  • Advances in autoimmune encephalitis studies in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to the disorder. The disorder or syndrome has been linked to a wide variety of pathologic processes associated with the neuron-specific autoantibodies targeting intracellular and plasma membrane antigens. However, current criteria for autoimmune encephalitis are quite dependent on antibody testing and responses to immunotherapy, which might delay the diagnosis. This form of encephalitis can involve the multifaceted presentation of seizures and unexpected behavioral changes. The spectrum of neuropsychiatric symptoms in children is less definitive than that in adults, and the incorporation of clinical, immunological, electrophysiological, and neuroradiological results is critical to the diagnostic approach. In this review, we document the clinical and immunologic characteristics of autoimmune encephalitis known to date, with the goal of helping clinicians in differential diagnosis and to provide prompt and effective treatment.

Biochemical and Biophysical Characterizations of the Interaction between Two PDZ Adapter Proteins NHERF and E3KARP in vitro

  • Hwang, Eun-Young;Jeong, Mi-Suk;Jang, Se-Bok
    • Bulletin of the Korean Chemical Society
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    • 제31권11호
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    • pp.3241-3246
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    • 2010
  • NHERF ($Na^+/H^+$ exchanger regulatory factor) and E3KARP (NHE3 kinase A regulatory protein) play important roles in membrane targeting, trafficking and sorting of ion channels, transmembrane receptors and signaling proteins in many tissues. Each of these proteins contains two PDZ (PSD-95/Dlg-1/ZO-1) domains, which mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. The interaction between NHERF and E3KARP was investigated by surface plasmon resonance spectroscopy (BIAcore), fluorescence measurement, His-tagged pull-down experiment, and size-exclusion column (SEC) chromatography. BIAcore experiments revealed that NHERF bound to E3KARP with an apparent $K_D$ of 7 nM. Fluorescence emission spectra of the NHERF-E3KARP complex suggested that the tight interaction between these proteins was accompanied by significant conformational changes in one or both. The CD spectra of NHERF and E3KARP show that the conformational changes of these proteins were dependent on pH and temperature. These results implicate that the NHERF-E3KARP complex allows intracellular signaling complexes to form through PDZ-PDZ interactions.

근세포 분화에 관한 연구 계배의 Myoblasts에 있어서 Protein Kinase C (PKC)의 인 산화작용과 Down Regulation (Studies on the Differentiation of Skeletal Muscle Cells in uitro : The Phosphorylation and Down Regulation of Protein Kinase C in Myoblasts of Chick Embryos)

  • 문현근;최원철
    • 한국동물학회지
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    • 제35권2호
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    • pp.161-172
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    • 1992
  • In the short-term treahent of 12-0-tetradecanoylphorbol-13-acetate (TPA) or platelet-derived growth factor (PDGF), the'Wh and PDGF induced the Protein Kinase C (PKC) activation and migration from the cytoplasm to the peripheral nulcear membrane. And the activated PKC which was directly or indirectly stimulated by TPA or PDGF Phosphorylated many kinds of PKC's targeting proteins and induces various biological responses. Especially, the cytoplasmic PKC was phosphorylated within 1 hr and 10 min by TPA-and PDGF-treahent respectivelv. In the long-term treatment of TPA or PDGF, both of them induced the down-regulation and translocation of PKC in the mvoblasts. The down-regulation of PKC isozyrnes, the pattern of PKC I and ll was similar to the PKC 111 isozpnes in the cytoplasm. But in the nucleolus, the TPA did not induce and down-regulation or the inhibition of the immunoreactivity of PKC III antibody. This investigation indicates that each isozvmes of PKC mal be performed the different effects to the down-regulation of the cytoplasm or nucleolus. And douvn-regulated myoblasts contained low immunoreactivity of PKC antibodies.

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Proteins as the molecular markers of male fertility

  • Beeram, Eswari
    • 식품보건융합연구
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    • 제4권4호
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    • pp.18-25
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    • 2018
  • Proteins play a key role in many functions such as metabolic activity, differentiation, as cargos and cell fate regulators. It is necessary to know about the markers involved in male fertility in order to develop remedies for the treatment of male infertility. But, the role of the proteins is not limited to particular function in the biological systems. Some of the proteins act as ion channels such as catsper and proteins like Nanos acts as a translational repressor in germ cells and expressed in prenatal period whose role in male fertility is uncertain. Rbm5 is a pre mRNA splicing factor necessary for sperm differentiation whose loss of function results deficit in sperm production. DEFB114 is a beta defensin family protein necessary for sperm motility in LPS challenged mice where as TEX 101 is a plasma membrane specific germ cell protein whose function is not clearly known u to now. Gpr56 is another adhesion protein whose null mutation leads to arrest of production of pups in rats. Amyloid precursor protein role in Alzheimer's disease is already known but it plays an important role in male fertility also but its function is uncertain and has to be considered while targeting APP during the treatment of Alzheimer's disease. The study on amyloid precursor protein in male fertility is a novel thing but requires further study in correlation to alzheimer's disease.

The Transport of Organic Cations in the Small Intestine: Current Knowledge and Emerging Concepts

  • Kim, Moon-Kyoung;Shim, Chang-Koo
    • Archives of Pharmacal Research
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    • 제29권7호
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    • pp.605-616
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    • 2006
  • A wide variety of drugs and endogenous bioactive amines are organic cations (OCs). Approximately 40% of all conventional drugs on the market are OCs. Thus, the transport of xenobiotics or endogenous OCs in the body has been a subject of considerable interest, since the discovery and cloning of a family of OC transporters, referred to as organic cation transporter (OCTs), and a new subfamily of OCTs, OCTNs, leading to the functional characterization of these transporters in various systems including oocytes and some cell lines. Organic cation transporters are critical in drug absorption, targeting, and disposition of a drug. In this review, the recent advances in the characterization of organic cation transporters and their distribution in the small intestine are discussed. The results of the in vitro transport studies of various OCs in the small intestine using techniques such as isolated brush-border membrane vesicles, Ussing chamber systems and Caco-2 cells are discussed, and in vivo knock-out animal studies are summarized. Such information is essential for predicting pharmacokinetics and pharmacodynamics and in the design and development of new cationic drugs. An understanding of the mechanisms that control the intestinal transport of OCs will clearly aid achieving desirable clinical outcomes.

Cell Surface Antigen Display for Neuronal Differentiation-Specific Tracking

  • Kim, Sang Chul;Lee, Eun-Hye;Yu, Ji Hea;Kim, Sang-Mi;Nam, Bae-Geun;Chung, Hee Yong;Kim, Yeon-Soo;Cho, Sung-Rae;Park, Chang-Hwan
    • Biomolecules & Therapeutics
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    • 제27권1호
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    • pp.78-84
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    • 2019
  • Cell therapeutic agents for treating degenerative brain diseases using neural stem cells are actively being developed. However, few systems have been developed to monitor in real time whether the transplanted neural stem cells are actually differentiated into neurons. Therefore, it is necessary to develop a technology capable of specifically monitoring neuronal differentiation in vivo. In this study, we established a system that expresses cell membrane-targeting red fluorescent protein under control of the Synapsin promoter in order to specifically monitor differentiation from neural stem cells into neurons. In order to overcome the weak expression level of the tissue-specific promoter system, the partial 5' UTR sequence of Creb was added for efficient expression of the cell surface-specific antigen. This system was able to track functional neuronal differentiation of neural stem cells transplanted in vivo, which will help improve stem cell therapies.

Solution Plasma Synthesis of BNC Nanocarbon for Oxygen Reduction Reaction

  • Lee, Seung-Hyo
    • 한국표면공학회지
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    • 제51권5호
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    • pp.332-336
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    • 2018
  • Alkaline oxygen electrocatalysis, targeting anion exchange membrane alkaline-based metal-air batteries has become a subject of intensive investigation because of its advantages compared to its acidic counterparts in reaction kinetics and materials stability. However, significant breakthroughs in the design and synthesis of efficient oxygen reduction catalysts from earth-abundant elements instead of precious metals in alkaline media still remain in high demand. One of the most inexpensive alternatives is carbonaceous materials, which have attracted extensive attention either as catalyst supports or as metal-free cathode catalysts for oxygen reduction. Also, carbon composite materials have been recognized as the most promising because of their reasonable balance between catalytic activity, durability, and cost. In particular, heteroatom (e.g., N, B, S or P) doping on carbon materials can tune the electronic and geometric properties of carbon, providing more active sites and enhancing the interaction between carbon structure and active sites. Here, we focused on boron and nitrogen doped nanocarbon composit (BNC nanocarbon) catalysts synthesized by a solution plasma process using the simple precursor of pyridine and boric acid without further annealing process. Additionally, guidance for rational design and synthesis of alkaline ORR catalysts with improved activity is also presented.

Anti-Inflammatory Role of TAM Family of Receptor Tyrosine Kinases Via Modulating Macrophage Function

  • Lee, Chang-Hee;Chun, Taehoon
    • Molecules and Cells
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    • 제42권1호
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    • pp.1-7
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    • 2019
  • Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.

Photocatalytic degradation of organic compounds by 2-ethylimidazole-treated titania under visible light illumination

  • Seo, Jiwon;Jeong, Junyoung;Lee, Changha
    • Membrane and Water Treatment
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    • 제10권3호
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    • pp.223-229
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    • 2019
  • Titania modified by 2-ethylimidazole (2-EI) (denoted as $2-EI-TiO_2$) demonstrated visible light photocatalytic activity for the degradation of organic compounds. $2-EI-TiO_2$ was a bright brown powder that exhibited similar crystallinity and morphology with the control $TiO_2$. A diffuse reflectance spectrum indicated that $2-EI-TiO_2$ absorbs visible light of all wavelengths. X-ray photoelectron spectroscopy (XPS) confirmed the cationic state of nitrogen species (e.g. Ti-O-N) on the surface of $2-EI-TiO_2$. Visible light-illuminated $2-EI-TiO_2$ degraded $10{\mu}M$ 4-chlorophenol (4-CP) by approximately 85% in 4 h. The photochemical activity of $2-EI-TiO_2$ was selective in targeting the organic compound. The repeated use of $2-EI-TiO_2$ decreased the photocatalytic activity for the 4-CP degradation. Experiments using radical scavengers and oxidant probes revealed that the oxidation by photogenerated holes is responsible for the degradation of organic compounds by illuminated $2-EI-TiO_2$ and the role of $^{\bullet}OH$ is negligible.

The role of the voltage-gated potassium channel, Kv2.1 in prostate cancer cell migration

  • Park, Hyun Woo;Song, Min Seok;Sim, Hun Ju;Ryu, Pan Dong;Lee, So Yeong
    • BMB Reports
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    • 제54권2호
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    • pp.130-135
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    • 2021
  • Voltage-gated potassium (Kv) channels are involved in many important cellular functions and play pivotal roles in cancer progression. The expression level of Kv2.1 was observed to be higher in the highly metastatic prostate cancer cells (PC-3), specifically in their membrane, than in immortalized prostate cells (WPMY-1 cells) and comparatively less metastatic prostate cancer cells (LNCaP and DU145 cells). However, Kv2.1 expression was significantly decreased when the cells were treated with antioxidants, such as N-acetylcysteine or ascorbic acid, implying that the highly expressed Kv2.1 could detect reactive oxygen species (ROS) in malignant prostate cancer cells. In addition, the blockade of Kv2.1 with stromatoxin-1 or siRNA targeting Kv2.1 significantly inhibited the migration of malignant prostate cancer cells. Our results suggested that Kv2.1 plays an important role as a ROS sensor and that it is a promising therapeutic molecular target in metastasis of prostate cancer.