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https://www.readbyqxmd.com/read/28647135/ultrasound-dependent-cytoplasmic-internalization-of-a-peptide-sonosensitizer-conjugate
#1
Yuki Inaba, Kazunori Watanabe, Mizuki Kitamatsu, Eiji Nakata, Atsushi Harada, Takashi Ohtsuki
A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells...
June 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28645727/inhibition-of-non-canonical-hiv-1-tat-secretion-through-the-cellular-na-k-atpase-blocks-hiv-1-infection
#2
Silvia Agostini, Hashim Ali, Chiara Vardabasso, Antonio Fittipaldi, Ennio Tasciotti, Anna Cereseto, Antonella Bugatti, Marco Rusnati, Marina Lusic, Mauro Giacca
Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na(+),K(+)-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity...
June 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28641785/acute-detachment-of-hexokinase-ii-from-mitochondria-modestly-increases-oxygen-consumption-of-the-intact-mouse-heart
#3
Rianne Nederlof, Simone Denis, Benjamin Lauzier, Christine Des Rosiers, Markku Laakso, Jacob Hagen, Carmen Argmann, Ronald Wanders, Riekelt H Houtkooper, Markus W Hollmann, Sander M Houten, Coert J Zuurbier
OBJECTIVE: Cardiac hexokinase II (HKII) can translocate between cytosol and mitochondria and change its cellular expression with pathologies such as ischemia-reperfusion, diabetes and heart failure. The cardiac metabolic consequences of these changes are unknown. Here we measured energy substrate utilization in cytosol and mitochondria using stabile isotopes and oxygen consumption of the intact perfused heart for 1) an acute decrease in mitochondrial HKII (mtHKII), and 2) a chronic decrease in total cellular HKII...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28638371/the-anticancer-peptide-tat-rasgap317-326-exerts-broad-antimicrobial-activity
#4
Mathieu Heulot, Nicolas Jacquier, Sébastien Aeby, Didier Le Roy, Thierry Roger, Evgeniya Trofimenko, David Barras, Gilbert Greub, Christian Widmann
Antibiotic resistance has become a major health issue. Nosocomial infections and the prevalence of resistant pathogenic bacterial strains are rising steadily. Therefore, there is an urgent need to develop new classes of antibiotics effective on multi-resistant nosocomial pathogenic bacteria. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, induces cancer cell death, inhibits metastatic progression, and sensitizes tumor cells to various anti-cancer treatments in vitro and in vivo...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28630469/c2238-anp-gene-variant-promotes-increased-platelet-aggregation-through-the-activation-of-nox2-and-the-reduction-of-camp
#5
Roberto Carnevale, Pasquale Pignatelli, Giacomo Frati, Cristina Nocella, Rosita Stanzione, Daniele Pastori, Simona Marchitti, Valentina Valenti, Maria Santulli, Emanuele Barbato, Teresa Strisciuglio, Leonardo Schirone, Carmine Vecchione, Francesco Violi, Massimo Volpe, Speranza Rubattu, Sebastiano Sciarretta
Subjects carrying the C2238 variant of the atrial natriuretic peptide (ANP) gene have a higher occurrence of stroke and acute coronary syndrome, suggesting an increased predisposition to acute thrombotic events in these subjects. We evaluated for the first time the direct effects of mutant ANP (C2238/αANP) on platelet activation in vitro and in human subjects. In vitro, platelets were incubated with no peptide, with T2238/αANP (WT) or with C2238/αANP at different concentrations. C2238/αANP (10(-10) M) induced higher collagen-induced platelet aggregation with respect to both control without ANP and T2238/αANP...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625985/periplasmic-nicotine-dehydrogenase-ndhab-utilizes-pseudoazurin-as-its-physiological-electron-acceptor-in-agrobacterium-tumefaciens-s33
#6
Wenjun Yu, Rongshui Wang, Haiyan Huang, Huijun Xie, Shuning Wang
Agrobacterium tumefaciens S33 can grow with nicotine as the sole source of carbon, nitrogen, and energy via a novel hybrid of the pyridine pathway and the pyrollidine pathway. Characterization of the enzymes involved in the hybrid pathway is important for understanding its biochemical mechanism. Here we report that the molybdenum-containing nicotine dehydrogenase (NdhAB), which catalyzes the initial step of nicotine degradation, is located in the periplasm of strain S33, while the 6-hydroxynicotine oxidase and 6-hydroxypseudooxynicoine oxidase are in the cytoplasm...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28625133/recent-advances-in-targeting-the-hiv-1-tat-tar-complex
#7
Fardokht A Abulwerdi, Stuart F J Le Grice
Following seminal discoveries by Rosen and co-workers in 1985, the HIV-1 TAR has emerged as one of the most extensively studied regulatory elements of the HIV-1 genome. Located adjacent to the long terminal repeat promoter, this cis-acting motif, in conjunction with the viral Tat protein, plays a critical role in viral genomic RNA synthesis via modification of the transcription complex. As such, the Tat/TAR axis has been the subject of intense efforts aimed at developing therapeutic interventions, directed against both the protein and nucleic acid components...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28623271/decoy-peptide-targeted-to-toll-il-1r-domain-inhibits-lps-and-tlr4-active-metabolite-morphine-3-glucuronide-sensitization-of-sensory-neurons
#8
Yohance M Allette, Youngsook Kim, Aaron L Randolph, Jared A Smith, Matthew S Ripsch, Fletcher A White
Accumulating evidence indicates that Toll-like receptor (TLR) signaling adapter protein interactions with Toll/Interleukin-1 Receptor (TIR) domains present in sensory neurons may modulate neuropathic pain states. Following ligand interaction with TLRs, TIR serves to both initiate intracellular signaling and facilitate recruitment of signaling adapter proteins to the intracytoplasmic domain. Although TLR TIR is central to a number of TLR signaling cascades, its role in sensory neurons is poorly understood. In this study we investigated the degree to which TLR TIR decoy peptide modified to include a TAT sequence (Trans-Activator of Transcription gene in HIV; TAT-4BB) affected LPS-induced intracellular calcium flux and excitation in sensory neurons, and behavioral changes due to TLR4 active metabolite, morphine-3-glucuronide (M3G) exposure in vivo...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619171/proteomic-and-bioinformatic-analyses-of-putative-mannheimia-haemolytica-secretome-by-liquid-chromatography-and-tandem-mass-spectrometry
#9
Sahlu Ayalew, Anthony W Confer, Steve D Hartson, Patricia J Canaan, Mark Payton, Brian Couger
Mannheimia haemolytica is a major bacterial contributor to bovine respiratory disease complex that costs the livestock industry a billion dollars a year in USA. Commercial vaccines are only partially efficacious under field conditions. Earlier studies found that outer membrane protein preparations and culture supernatants can induce immune responses that enhance resistance to challenge by M. haemolytica strains. The objective of this study was to characterize secretome of two M. haemolytica stains grown under two different media...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28606781/sab-is-differentially-expressed-in-the-brain-and-affects-neuronal-activity
#10
Alejandro O Sodero, Monica Rodriguez-Silva, Chiara Salio, Marco Sassoè-Pognetto, Jeremy W Chambers
Sab (SH3 binding protein 5 or SH3BP5) is a mitochondrial scaffold protein involved in signaling associated with mitochondrial dysfunction and apoptosis; furthermore, Sab is a crucial signaling platform for neurodegenerative disease. To determine how this signaling nexus could have a significant effect on disease, we examined the regional abundance of Sab in the brain and sub-neuronal distribution, and we monitored the effect of Sab-mediated signaling on neuronal activity. We found that Sab is widely expressed in the adult mouse brain with increased abundance in hippocampus, ventral midbrain, and cerebellum...
June 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28604448/map2k6-fp-enhances-the-sensitiveness-of-paclitaxel-for-ovarian-cancer-via-inducing-autophagy
#11
Ying Guo, Jin Yuan, Shuqin Yin, Xiaoxia Wang, Rong Shuai, Jiali Kang
BACKGROUND: Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Recent studies have revealed an association between autophagy and drug resistance. METHODS: We previously synthesized a MAPK kinase-recombinant fusion protein, MAP2K6-FP, that contains 3 domains: a protein transduction domain TAT, a human ovarian cancer HO8910 cell-specific binding peptide, and a potential antitumor effector domain MKK6(E)...
June 10, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28602843/combination-of-cell-penetrating-peptides-and-heterologous-dna-prime-protein-boost-strategy-enhances-immune-responses-against-hiv-1-nef-antigen-in-balb-c-mouse-model
#12
Somayeh Kadkhodayan, Behnaz Sadat Jafarzade, Seyed Mehdi Sadat, Fateme Motevalli, Elnaz Agi, Azam Bolhassani
To develop a strong HIV specific T-cell response, the HIV-1 Tat and Nef regulatory proteins have been known as attractive antigenic candidates in vaccine design. A peptide transduction domain of Tat (48-60 aa) could act to deliver other therapeutic molecules into different cells. In this line, several cell-penetrating peptides (CPPs) have been designed to transfer DNA, siRNA, polypeptides and proteins into cells through non-covalent approach such as CADY and PEP families. Some studies showed that the endogenous adjuvants including heat shock protein Gp96 could stimulate antigen-specific T cell immune responses...
June 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28593564/activation-of-adrenergic-receptor-in-h9c2-cardiac-myoblasts-co-stimulates-nox2-and-the-derived-ros-mediate-the-downstream-responses
#13
Nikhat Saleem, Shyamal K Goswami
In recent years, NADPH oxidases (Noxes) have emerged as an important player in cardiovascular pathophysiology. Despite the growing evidences on the role of specific Nox isoforms, mechanisms of their activation, targets of reactive oxygen species (ROS) generated, and their downstream effects are poorly understood as yet. In this study, we treated H9c2 cardiac myoblasts with norepinephrine (NE, 2 µM), inducing ROS generation that was inhibited by Nox2-specific peptide inhibitor gp91ds-tat. Organelle-specific hydrogen peroxide-sensitive probe HyPer showed that the site of ROS generation is primarily in the cytosol, to some extent in the endoplasmic reticulum (ER) but not the mitochondria...
June 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28589421/tat-myod-fused-proteins-together-with-c2c12-conditioned-medium-are-able-to-induce-equine-adult-mesenchimal-stem-cells-towards-the-myogenic-fate
#14
Marco Patruno, Chiara Gomiero, Roberta Sacchetto, Ohad Topel, Alessandro Negro, Tiziana Martinello
The Tat protein is able to translocate through the plasma membrane and when it is fused with other peptides may acts as a protein transduction system. This ability appears particularly interesting to induce tissue-specific differentiation when the Tat protein is associated to transcription factors. In the present work, the potential of the complex Tat-MyoD in inducing equine peripheral blood mesenchymal stem cells (PB-MSCs) towards the myogenic fate, was evaluated. Results showed that the internalization process of Tat-MyoD happens only in serum free conditions and that the nuclear localization of the fused complex is observed after 15 hours of incubation...
June 6, 2017: Veterinary Research Communications
https://www.readbyqxmd.com/read/28570804/self-assembled-dna-dendrimer-nanoparticle-for-efficient-delivery-of-immunostimulatory-cpg-motifs
#15
Yijiao Qu, Juanjuan Yang, Pengfei Zhan, Shaoli Liu, Kun Zhang, Qiao Jiang, Can Li, Baoquan Ding
Dendrimer-like DNA nanostructures have attractive properties such as mechanical stability, highly branched nanostructure, customized sizes, and biocompatibility. In this study, we construct programmable DNA dendrimeric nanoparticles as efficient vehicles to deliver immunostimulatory cytosine-phosphate-guanosine (CpG) sequences for activation of the immune response. DNA dendrimers decorated with CpG-containing hairpin-loops triggered stronger immune response characterized by pro-inflammatory cytokines production, in contrast to DNA dendrimers loading linear CpG...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28530637/cell-penetrating-peptides-selectively-targeting-smad3-inhibit-profibrotic-tgf-%C3%AE-signaling
#16
Jeong-Han Kang, Mi-Yeon Jung, Xueqian Yin, Mahefatiana Andrianifahanana, Danielle M Hernandez, Edward B Leof
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28515319/the-h-region-of-twin-arginine-signal-peptides-supports-productive-binding-of-bacterial-tat-precursor-proteins-to-the-tatbc-receptor-complex
#17
Agnes Ulfig, Julia Fröbel, Frank Lausberg, Anne-Sophie Blümmel, Anna Katharina Heide, Matthias Müller, Roland Freudl
The twin arginine translocation (Tat) pathway transports folded proteins across bacterial membranes. Tat precursor proteins possess a conserved twin-arginine (RR) motif in their signal peptides that is involved in their binding to the Tat translocase, but some facets of this interaction remain unclear. Here, we investigated the role of the hydrophobic (h-) region of the Escherichia coli TMAO reductase (TorA) signal peptide in TatBC receptor binding in vivo and in vitro. We show that besides the RR motif, a minimal functional h-region in the signal peptide is required for Tat-dependent export in E...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28490747/structural-basis-for-importin-%C3%AE-binding-of-the-human-immunodeficiency-virus-tat
#18
K M Smith, Z Himiari, S Tsimbalyuk, J K Forwood
HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning (48)GRKKRR, and a cell penetrating peptide (CPP) signal spanning (48)GRKKRRQRRRAPQN...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483976/targeting-a-potassium-channel-syntaxin-interaction-ameliorates-cell-death-in-ischemic-stroke
#19
Chung-Yang Yeh, Ashlyn M Bulas, Aubin Moutal, Jami L Saloman, Karen A Hartnett, Charles T Anderson, Thanos Tzounopoulos, Dandan Sun, Rajesh Khanna, Elias Aizenman
The voltage-gated K(+) channel Kv2.1 has been intimately linked with neuronal apoptosis. After ischemic, oxidative, or inflammatory insults, Kv2.1 mediates a pronounced, delayed enhancement of K(+) efflux, generating an optimal intracellular environment for caspase and nuclease activity, key components of programmed cell death. This apoptosis-enabling mechanism is initiated via Zn(2+)-dependent dual phosphorylation of Kv2.1, increasing the interaction between the channel's intracellular C-terminus domain and the SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) protein syntaxin 1A...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28482272/screening-of-commercial-cyclic-peptide-conjugated-to-hiv-1-tat-peptide-as-inhibitor-of-n-terminal-heptad-repeat-glycoprotein-2-ectodomain-ebola-virus-through-in-silico-analysis
#20
Usman Sumo Friend Tambunan, Ahmad Husein Alkaff, Mochammad Arfin Fardiansyah Nasution, Arli Aditya Parikesit, Djati Kerami
Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism...
April 21, 2017: Journal of Molecular Graphics & Modelling
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