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Translocator protein

Daniela Sorriento, Gaetano Santulli, Michele Ciccarelli, Angela Serena Maione, Maddalena Illario, Bruno Trimarco, Guido Iaccarino
We have recently demonstrated that the amino-terminal domain of G protein coupled receptor kinase (GRK) type 5, (GRK5-NT) inhibits NFκB activity in cardiac cells leading to a significant amelioration of LVH. Since GRK5-NT is known to bind calmodulin, this study aimed to evaluate the functional role of GRK5-NT in the regulation of calcium-calmodulin-dependent transcription factors. We found that the overexpression of GRK5-NT in cardiomyoblasts significantly reduced the activation and the nuclear translocation of NFAT and its cofactor GATA-4 in response to phenylephrine (PE)...
March 15, 2018: International Journal of Molecular Sciences
Dehbia Benkerrou, Matteo Ceccarelli
One of the greatest health threats facing modern medicine is the emergence of new bacterial strains which are increasingly resistant to almost all currently available antibiotics. According to a CDC (Center for Disease Control and Prevention) report published in 2013, 63% of Acinetobacter species have been identified as Multidrug resistant strains. As for other Gram-negative bacteria, the presence of an outer membrane increases the intrinsic resistance of A. baumannii to most antibiotics. The outer membrane of A...
March 15, 2018: Physical Chemistry Chemical Physics: PCCP
Wen Zhang, Jun-Ke Song, Rong Yan, Li Li, Zhi-Yong Xiao, Wen-Xia Zhou, Zhen-Zhong Wang, Wei Xiao, Guan-Hua Du
Diterpene ginkgolides meglumine injection (DGMI) is a therapeutic extract of Ginkgo biloba L, which has been used for the treatment of cerebral ischemic stroke in China. Ginkgolides A, B and C are the main components of DGMI. This study was designed to investigate the neuroprotective effects of DGMI components against ischemic stroke in vivo and in vitro. Acute cerebral ischemic injury was induced in rats by occlusion of the middle cerebral artery (MCA) for 1.5 h followed by 24 h reperfusion. The rats were treated with DGMI (1, 3 and 10 mg/kg, iv) at the onset of reperfusion and 12 h after reperfusion...
March 15, 2018: Acta Pharmacologica Sinica
Yawen Li, Fangming Xiu, Zezhong Mou, Zhiwei Xue, Huanhui Du, Chunxue Zhou, Yan Li, Yongyu Shi, Shenyi He, Huaiyu Zhou
AIM: Exosomes are nanoscale membranous vesicles secreted by most cell types able to transfer bioactive molecules among cells, which play crucial roles in intercellular communication. We characterized the exosomes derived from Toxoplasma gondii (T. gondii) and detected the immune response in macrophages. METHODS: We used transmission electron microscopy, nanotracking analysis and western blotting to identify T. gondii exosomes. Functional experiments were performed in RAW264...
March 15, 2018: Nanomedicine
Charles K Davis, Sreekala S Nampoothiri, G K Rajanikant
The constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential to PHD2, FIH, and pVHL was further verified by re-docking, molecular dynamics (MD) simulation and by Drug Affinity Responsive Target Stability (DARTS) assay...
March 14, 2018: Molecular Neurobiology
Marjan Nokhbehsaim, Svenja Memmert, Anna Damanaki, Shanika Nanayakkara, Xiaoyan Zhou, Andreas Jäger, James Deschner
OBJECTIVES: Periodontopathogens induce immunoinflammatory responses characterized by the release of inflammatory mediators, e.g., interleukin (IL)-1β, IL-6, and IL-8. Ghrelin (GHRL) is an appetite hormone which mediates its effect via the functional receptor GHS-R1a. This study was to examine the effect of an inflammatory insult on GHS-R1a in human periodontal cells. MATERIALS AND METHODS: Periodontal ligament (PDL) cells and gingival fibroblasts (HGFs) were exposed to IL-1β in the presence and absence of GHRL...
March 14, 2018: Clinical Oral Investigations
Neydher Berroterán-Infante, Theresa Balber, Petra Fürlinger, Michael Bergmann, Rupert Lanzenberger, Marcus Hacker, Markus Mitterhauser, Wolfgang Wadsak
The overexpression of the translocator protein (TSPO) has been amply reported for a variety of conditions, including neurodegenerative disorders, heart failure, and cancer. Thus, TSPO has been proposed as an excellent imaging biomarker, allowing, in this manner, to obtain an accurate diagnosis and to follow disease progression and therapy response. Accordingly, several radioligands have been developed to accomplish this purpose. In this work, we selected [18 F]FEPPA, as one of the clinical established tracers, and assessed its in vitro performance in colorectal cancer...
March 8, 2018: ACS Medicinal Chemistry Letters
Joy Ogbechi, Belinda S Hall, Thomas Sbarrato, Jack Taunton, Anne E Willis, Ronald C Wek, Rachel E Simmonds
Mycolactone is the exotoxin virulence factor of Mycobacterium ulcerans that causes the neglected tropical disease Buruli ulcer. We recently showed it to be a broad spectrum inhibitor of Sec61-dependent co-translational translocation of proteins into the endoplasmic reticulum (ER). An outstanding question is the molecular pathway linking this to its known cytotoxicity. We have now used translational profiling to better understand the reprogramming that occurs in cells exposed to mycolactone. Gene ontology identified enrichment in genes involved in cellular response to stress, and apoptosis signalling among those showing enhanced translation...
March 14, 2018: Cell Death & Disease
Susan E Hepp, Gina M Borgo, Simina Ticau, Taro Ohkawa, Matthew D Welch
The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the type species of alphabaculoviruses, is an enveloped DNA virus that infects lepidopteran insects and is commonly known as a vector for protein expression and cell transduction. AcMNPV belongs to a diverse group of viral and bacterial pathogens that target the host cell actin cytoskeleton during infection. AcMNPV is unusual, however, in that it absolutely requires actin translocation into the nucleus early in infection, and actin polymerization within the nucleus late in infection coincident with viral replication...
March 14, 2018: Journal of Virology
Randall Marcelo Chin, Tadas Panavas, Jeffrey M Brown, Krista K Johnson
Mitochondrial disease may be caused by mutations in the protein-coding genes of the mitochondrial genome. A promising strategy for treating such diseases is allotopic expression-the translation of wild-type copies of these proteins in the cytosol, with subsequent translocation into the mitochondria, resulting in rescue of mitochondrial function. In this paper, we develop an automated, quantitative, and unbiased screening platform to evaluate protein localization and mitochondrial morphology. This platform was used to compare 31 mitochondrial targeting sequences and 15 3' UTRs in their ability to localize up to 9 allotopically expressed proteins to the mitochondria and their subsequent impact on mitochondrial morphology...
March 13, 2018: Cell Reports
Liang Weng, Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi
Amino acid signaling mediated by the activation of mechanistic target of rapamycin complex 1 (mTORC1) is fundamental to cell growth and metabolism. However, how cells negatively regulate amino acid signaling remains largely unknown. Here, we show that interaction between 4F2 heavy chain (4F2hc), a subunit of multiple amino acid transporters, and the multifunctional hub protein girders of actin filaments (Girdin) down-regulates mTORC1 activity. 4F2hc interacts with Girdin in mitogen-activated protein kinase (MAPK)- and amino acid signaling-dependent manners to translocate to the lysosome...
March 14, 2018: PLoS Biology
Yang Yuan, Shan-Shan Pan
BACKGROUND: Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in EP-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene-encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria. METHODS: Our exercise preconditioning (EP) protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP...
March 9, 2018: Journal of Cardiovascular Pharmacology
Alfredo Perales-Puchalt, Jairo Perez-Sanz, Kyle K Payne, Nikolaos Svoronos, Michael J Allegrezza, Ricardo A Chaurio, Carmen Anadon, Joseph Calmette, Subir Biswas, Jessica A Mine, Tara Lee Costich, Logan Nickels, Jayamanna Wickramasinghe, Melanie R Rutkowski, Jose R Conejo-Garcia
Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacerbate mucosal damage. Restoration of the microbiota through fecal-pellet gavage drives healing of cisplatin-induced intestinal damage. Bacterial translocation to the blood stream is correspondingly abrogated, resulting in a significant reduction in systemic inflammation, as evidenced by decreased serum IL-6 and reduced mobilization of granulocytes...
March 14, 2018: Journal of Leukocyte Biology
Aldo Eugenio Rossini, Fabrizio Gala, Mauro Chinappi, Giuseppe Zollo
Solid-state nanopores and nanogaps are emerging as promising tools for single molecule analysis. 2D materials, such as graphene, can potentially reach the spatial resolution needed for nucleic acid and protein sequencing. In the context of the density functional theory, atomistic modeling and non-equilibrium Green's function calculation, we show that glycine based polypeptide chains translocating across a nano-gap between two semi-infinite graphene nano-ribbons leave a specific transverse current signature for each peptide bond...
March 14, 2018: Nanoscale
Peng Yin, Guizhen Song, Zhenhua Jiang
PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytotoxic platinum-based drug used for chemotherapy of different types of human cancers such as NPC. Nevertheless, the effects of CIS on the migration and invasion of human NPC cells and the underlying molecular mechanisms have not yet been fully scrutinized...
March 14, 2018: Cancer Chemotherapy and Pharmacology
Bo Hou, Eyleen S Heidrich, Denise Mehner-Breitfeld, Thomas Brüser
The twin-arginine translocation (Tat) system that comprises the TatA, TatB, and TatC components transports folded proteins across energized membranes of prokaryotes and plant plastids. It is not known, however, how the transport of this protein cargo is achieved. Favored models suggest that the TatA component supports transport by weakening the membrane upon full translocon assembly. Using Escherichia coli as model organism, we now demonstrate in vivo that the N-terminus of TatA can indeed destabilize the membrane, resulting in a lowered membrane energization in growing cells...
March 13, 2018: Journal of Biological Chemistry
Da Yeon Lee, Hwa Jin Lee, Jae-Ha Ryu
Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols ( 1 - 7 ) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, four prenylated polyphenols ( 2 - 4 and 6 ) with a catechol moiety efficiently suppressed the LPS-induced high level of NO with IC50 values of less than 6 µM. The compounds 2 - 4 and 6 also attenuated protein and mRNA levels of inducible nitric oxide synthase (iNOS)...
March 12, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
H Yu, H Wang, N Zhang, S M Gao, Y X Zhang
Objective: To study the correlation between expression of oncogene C-MYC protein and gene abnormality in diffuse large B-cell lymphoma (DLBCL). Methods: The expression of C-MYC protein and gene abnormality were detected by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, in 42 cases of paraffin-embedded DLBCL. All cases were collected at Department of Pathology, Weifang People's Hospital during January 2015 to October 2016. Results: The positive rate of C-MYC protein expression was 47...
March 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Shoji Segami, Mariko Asaoka, Satoru Kinoshita, Mayu Fukuda, Yoichi Nakanishi, Masayoshi Maeshima
Proton-translocating inorganic pyrophosphatase (H+-PPase) actively translocates protons across membranes coupled with the hydrolysis of inorganic pyrophosphate (PPi). H+-PPase, which is composed of a single protein and uses a simple compound as a substrate, has been recognized as a new type of ion pump in addition to the P-, F-, and V-type ion translocating ATPases. H+- and Na+-PPases are distributed in various organisms including plants, parasitic protozoa, Archaebacteria, and bacteria, but are not present in animals or yeast...
March 9, 2018: Plant & Cell Physiology
Shanshan Feng, Qiaozhi Zhou, Bo Yang, Qianqian Li, Aiqin Liu, Yingying Zhao, Changqing Qiu, Jun Ge, Huihong Zhai
BACKGROUND: Calcyclin Binding Protein/(Siah-1 interacting protein) (CacyBP/SIP) acts as an oncogene in colorectal cancer. The nuclear accumulation of CacyBP/SIP has been linked to the proliferation of cancer cells. It has been reported that intracellular Ca2+ induces the nuclear translocation of CacyBP/SIP. However, the molecular mechanism of CacyBP/SIP nuclear translocation has yet to be elucidated. The purpose of this study was to test whether the Ca2+-dependent binding partner S100 protein is involved in CacyBP/SIP nuclear translocation in colon cancer SW480 cells...
2018: PloS One
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