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Tat peptide

Hai-Hui Zhou, Li Zhang, Hai-Xia Zhang, Jin-Ping Zhang, Wei-Hong Ge
Transient global ischemia (TGI) is a major public health problem, and it heightens the need of effective treatments. The present study was undertaken to investigate whether recombinant polypeptide Tat-HA-NR2B9c improves spatial learning and memory deficits in rats after TGI. Rats were subjected to 20-min ischemia induced by four-vessel occlusion (4-VO) method and daily injected with Tat-HA-NR2B9c (1.12 mg/kg) for 1 week. Tat-HA-NR2B9c increased CREB activity, upregulated B-cell lymphoma-2 (Bcl-2) expression after treated for 24 h...
2017: Frontiers in Neurology
Jinming Zhang, Yifeng Zheng, Xi Xie, Lan Wang, Ziren Su, Yitao Wang, Kam W Leong, Meiwan Chen
Although tumor-targeting nanovehicles for hepatocellular carcinoma (HCC) chemotherapy have attracted great research and clinic interest, the poor cancer penetration, inefficient cellular uptake, and slow intracellular drug release greatly compromise their therapeutic outcomes. In this work, a multifunctional mixed micellar system, consisting of glycyrrhetinic acid (GA) for specific liver-targeting, trans-activator of transcription (TAT) peptide for potent cell penetration, and pH-sensitive poly(β-amino ester) polymers for acidic-triggered drug release, was developed to provide HCC-targeting delivery and pH-triggered release of doxorubicin (DOX)...
October 10, 2017: Molecular Pharmaceutics
Christina Amatya, Ilian A Radichev, Jacob Ellefson, Mark Williams, Alexei Y Savinov
Type 1 diabetes (T1D) is characterized by massive destruction of insulin-producing β cells by autoreactive T lymphocytes, arising via defective immune tolerance. Therefore, effective anti-T1D therapeutics should combine autoimmunity-preventing and insulin production-restoring properties. We constructed a cell-permeable PDX1-FOXP3-TAT fusion protein (FP) composed of two transcription factors: forkhead box P3 (FOXP3), the master regulator of differentiation and functioning of self-tolerance-promoting Tregs, and pancreatic duodenal homeobox-1 (PDX1), the crucial factor supporting β cell development and maintenance...
September 7, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Padmanabhan Mannangatti, Sammanda Ramamoorthy, Lankupalle Damodara Jayanthi
Amphetamine (AMPH)-mediated norepinephrine transporter (NET) downregulation requires NET-T258/S259 trafficking motif. The present study utilizes cell permeable NET-T258/S259 motif interfering peptide, which blocks AMPH-induced NET downregulation, to explore the role of this form of NET regulation in AMPH-mediated behaviors. In rats receiving intra-accumbal microinjections of TAT-conjugated peptides encompassing NET-T258/S259 motif, acute systemic AMPH failed to inhibit NE transport in the TAT-NET-T258/S259 wild-type (WT) peptide injected hemisphere but not in the vehicle or scrambled peptide injected hemisphere...
October 4, 2017: Neuropharmacology
Elena Britti, Fabien Delaspre, Anat Feldman, Melissa Osborne, Hagar Greif, Jordi Tamarit, Joaquim Ros
Friedreich ataxia (FA) is a rare disease caused by deficiency of frataxin, a mitochondrial protein. As there is no cure available for this disease, many strategies have been developed to reduce the deleterious effects of such deficiency. One of these approaches is based on delivering frataxin to the tissues by coupling the protein to trans-activator of transcription (TAT) peptides, which enables cell membranes crossing. In this study, we tested the efficiency of TAT-MTScs-FXN fusion protein to decrease neurodegeneration markers on frataxin-depleted neurons obtained from dorsal root ganglia (DRG), one of the most affected tissues...
October 5, 2017: Journal of Cellular and Molecular Medicine
Muhammad Jan Akhunzada, Balasubramanian Chandramouli, Nicholus Bhattacharjee, Sara Macchi, Francesco Cardarelli, Giuseppe Brancato
It is widely accepted that endocytosis mediates the uptake of cationic cell penetrating peptides (CPPs) at relatively low concentrations (i.e. nano- to micromolar), while direct transduction across the plasma membrane comes into play at higher concentrations (i.e. micro- to millimolar). This latter process appears to depend on peptide-driven cellular processes, which in turn may induce local perturbations of plasma-membrane composition and/or integrity, and to be favored by peptide aggregation, especially into dimers...
October 18, 2017: Physical Chemistry Chemical Physics: PCCP
Qian Li, Mengchuan Xu, Yali Cui, Chunqian Huang, Manji Sun
The membrane-permeable peptides (MPP) such as undecapeptides TAT (YGRKKRRQRRR) and CTP (YGRRARRRRRR) have been receiving much attention for delivering various kinds of low membrane-permeability materials in vitro and in vivo. We have successfully used MPP in carrying various proteins through blood-brain barrier (BBB) in treatment of many kinds of nervous diseases. However, people always concentrate their mind on the efficacy and the mechanism of permeation of the conjugates across BBB, but overlook the toxicity of the membrane-permeable peptide itself...
October 2017: Pharmacology Research & Perspectives
J M Schilling, A Kassan, C Mandyam, M L Pearn, A Voong, G G Grogman, V B Risbrough, I R Niesman, H H Patel, P M Patel, B P Head
Background: Isoflurane is widely used for anaesthesia in humans. Isoflurane exposure of rodents prior to post-natal day 7 (PND7) leads to widespread neurodegeneration in laboratory animals. Previous data from our laboratory suggest an attenuation of apoptosis with the p75 neurotrophin receptor (p75NTR) inhibitor TAT-Pep5. We hypothesized that isoflurane toxicity leads to behavioural and cognitive abnormalities and can be rescued with pre-anaesthesia administration of TAT-Pep5. Methods: Neonatal mouse pups were pretreated with either TAT-Pep5 (25 μl, 10 μM i...
September 1, 2017: British Journal of Anaesthesia
Diego Milani, Jane L Cross, Ryan S Anderton, David J Blacker, Neville W Knuckey, Bruno P Meloni
Following positive results with the poly-arginine peptide R18 when administered intravenously 30 or 60min after permanent and/or transient middle cerebral artery occlusion (MCAO; 90min) in the rat, we examined the effectiveness of the peptide when administered 2h after MCAO. R18 was administered intravenously (1000nmol/kg via jugular vein) after permanent MCAO or a transient 3-h MCAO or when administered intra-arterially (100nmol/kg via internal carotid artery) immediately after reperfusion following a transient 2-h MCAO...
September 28, 2017: Brain Research Bulletin
Neha Tiwari, Ankit Srivastava, Bishwajit Kundu, Manoj Munde
The heparin-protein interaction plays a vital role in numerous physiological and pathological processes. Not only is the binding mechanism of these interactions poorly understood, studies concerning their therapeutic targeting are also limited. Here, we have studied the interaction of the heparin interacting peptide (HIP) from Tat (which plays important role in HIV infections) with heparin. Isothermal titration calorimetry binding exhibits distinct biphasic isotherm with two different affinities in the HIP-heparin complex formation...
September 29, 2017: Journal of Molecular Recognition: JMR
Ji Hee Kang, Gantumur Battogtokh, Young Tag Ko
Despite potential applications of nucleic acid therapeutics, the lack of effective delivery systems hinders their clinical application. To overcome the barriers to nucleic acid delivery, we previously reported nanoparticles using phospholipid-polyethylenimine conjugates. However, toxicity of polyethylenimine remains as problematic issues. Herein, we proposed to substitute the polyethylenimine with arginine-rich peptide to obtain a less toxic carrier system. Nonaarginine was conjugated to the distal end of phospholipid hydrocarbon chains leading to phospholipid-nonaarginine conjugates (PL9R) and then lipid-peptide hybrid nanoparticles carrying oligonucleotide therapeutics (hNP) were constructed by self-assembly process...
September 27, 2017: Biomacromolecules
Yaqin Zhu, Jian Zhang, Fenghua Meng, Chao Deng, Ru Cheng, Jan Feijen, Zhiyuan Zhong
The application of cell-penetrating peptides like TAT for in vivo targeted delivery is limited because the penetration behavior is not cell-specific. Herein, we designed cRGD and TAT comodified cross-linkable micelles (cRGD/TAT CMs), in which the TAT peptide was shielded by relatively long poly(ethylene glycol) (PEG) chains. Docetaxel (DTX)-loaded cRGD/TAT CMs were very stable with minimal drug leakage under physiological conditions, whereas rapid DTX release took place in a reductive environment. Flow cytometry showed that the cRGD/TAT CMs with molar ratios of 20% cRGD and 10% TAT (cRGD20/TAT10 CMs) were selectively and efficiently taken up by ανβ3-overexpressing U87MG glioma cells, with 8...
October 18, 2017: ACS Applied Materials & Interfaces
Yufu Wang, Changcheng You, Rongzhi Wei, Jianing Zu, Chengchao Song, Jing Li, Jinglong Yan
With the emerging role of umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) for bone regeneration and delivery of therapeutic proteins, there is an increasing need for effective gene delivery systems to modify such cells. mTAT, a TAT peptide sequence bearing histidine and cysteine residues, has been successfully used for intracellular gene delivery. Using a gWiz-GFP plasmid, we demonstrated that polyethylenimine combined with mTAT (mTAT/PEI) displayed good transfection efficacy in hUCB-MSC. hUCB-MSC transfected with mTAT/PEI were shown to express more BMP-2 protein and mRNA, indicating the feasibility of using the cells as a BMP-2 delivery system...
2017: BioMed Research International
Xuefang Hao, Qian Li, Jintang Guo, Xiangkui Ren, Yakai Feng, Changcan Shi, Wencheng Zhang
Recently, gene therapy has attracted much attention, especially for the treatment of vascular disease. However, it is still challenging to develop the gene carriers with high biocompatibility as well as highly efficient gene delivery to overcome multiple barriers. Herein, a frequently used cell-penetrating peptide PKKKRKV (TAT) was selected as a functional sequence of the gene carrier with distinctive cell-penetrating ability. REDV peptide with selectively targeting function for endothelial cells (ECs) and nuclear localization signals (NLS) were integrated with this TAT peptide to obtain a highly efficient gene delivery system with ECs specificity and nucleus accumulation capacity...
October 18, 2017: ACS Applied Materials & Interfaces
Nataliya Sadekova, M Florencia Iulita, Diane Vallerand, Gervais Muhire, Mohamed Bourmoum, Audrey Claing, Hélène Girouard
BACKGROUND: Arterial stiffness is a risk factor for cognitive decline and dementia. However, its precise effects on the brain remain unexplored. Using a mouse model of carotid stiffness, we investigated its effect on glial activation and oxidative stress. METHODS: Arterial stiffness was induced by the application of calcium chloride to the adventitial region of the right carotid. Superoxide anion production, NADPH activity and levels, as well as glial activation were examined with immunohistochemical and biochemical approaches, 2-week postcalcification...
September 21, 2017: Journal of Hypertension
Seounghun Kang, Kyunglee Kang, Hyun Huh, Hyungjun Kim, Sung-Jin Chang, Tae Jung Park, Ki Soo Chang, Dal-Hee Min, Hongje Jang
Porous Au nanoplates (pAuNPs) were manufactured by a reducing agent-assisted galvanic replacement reaction on Ag nanoplates using a seed-mediated synthetic approach. Two core additives, poly(vinylpyrrolidone) and l-ascorbic acid, prevented fragmentation and proceeded secondary growth. By controlling the concentration of the additives and the amount of replacing ion AuCl4(-), various nanostructures including nanoplates with holes, nanoframes, porous nanoplates, and bumpy nanoparticles with unity and homogeneity were synthesized...
October 11, 2017: ACS Applied Materials & Interfaces
Thomas Démoulins, Thomas Ebensen, Kai Schulze, Pavlos C Englezou, Maria Pelliccia, Carlos A Guzmán, Nicolas Ruggli, Kenneth C McCullough
The major limitations with large and complex self-amplifying RNA vaccines (RepRNA) are RNase-sensitivity and inefficient translation in dendritic cells (DCs). Condensing RepRNA with polyethylenimine (PEI) gave positive in vitro readouts, but was largely inferior to virus-like replicon particles (VRP) or direct electroporation. In the present study, we improved such polyplex formulation and determined that fine-tuning of the polyplex structure is essential for ensuring efficacious translation. Thereby, three parameters dominate: (i) PEI molecular weight (MW); (ii) RepRNA:PEI (weight:weight) ratio; and (iii) inclusion of cell penetrating peptides (CPPs)...
September 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Rahajeng N Tunjungputri, Muhammad Hussein Gasem, Willemijn van der Does, Pandu H Sasongko, Bambang Isbandrio, Rolf T Urbanus, Philip G de Groot, Andre van der Ven, Quirijn de Mast
BACKGROUND: Severe leptospirosis is frequently complicated by a hemorrhagic diathesis, of which the pathogenesis is still largely unknown. Thrombocytopenia is common, but often not to the degree that spontaneous bleeding is expected. We hypothesized that the hemorrhagic complications are not only related to thrombocytopenia, but also to platelet dysfunction, and that increased binding of von Willebrand factor (VWF) to platelets is involved in both platelet dysfunction and increased platelet clearance...
September 2017: PLoS Neglected Tropical Diseases
Saliha Majdoul, Jérémie Cosette, Ababacar K Seye, Eric Bernard, Sophie Frin, Nathalie Holic, Nathalie Chazal, Laurence Briant, Lucile Espert, Anne Galy, David Fenard
Autophagy-related proteins such as Beclin1 are involved in an array of complex processes including antiviral responses, and may also modulate the efficiency of gene therapy viral vectors. The TatBeclin1 (TB1) peptide has been reported as an autophagy-inducing factor inhibiting the replication of pathogens such as HIV-1. Yet, autophagy-related proteins are also essential for the early steps of HIV-1 infection. Therefore, we examined here the effects of the Beclin1-evolutionarily conserved domain in TB1 on viral transduction and autophagy in single-round HIV infection or with nonreplicative HIV-1-derived lentiviral vectors (LV)...
September 19, 2017: Journal of Biological Chemistry
Mona Buhusi, Chris Etheredge, Ann-Charlotte Granholm, Catalin V Buhusi
Memory decline during aging or accompanying neurodegenerative diseases, represents a major health problem. Neurotrophins have long been considered relevant to the mechanisms of aging-associated cognitive decline and neurodegeneration. Mature Brain-Derived Neurotrophic Factor (BDNF) and its precursor (proBDNF) can both be secreted in response to neuronal activity and exert opposing effects on neuronal physiology and plasticity. In this study, biochemical analyses revealed that increased levels of proBDNF are present in the aged mouse hippocampus relative to young and that the level of hippocampal proBDNF inversely correlates with the ability to perform in a spatial memory task, the water radial arm maze (WRAM)...
2017: Frontiers in Aging Neuroscience
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