Palmitoylation as a Regulator of MAGUK Proteins Postsynaptic Localization

Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, and SAP97. They are present in the synapses and regulate the localization of synaptic proteins. Palmitoylation of PSD-95 has been demonstrated to involve in postsynaptic localization of PSD-95. SAP97 and PSD-93 contain palmitoylation sites that are very similar to PSD-95. However, the palmitoylation of SAP102 has not been fully studied. The proteomic analyses suggest the potential presence of palmitoylation of SAP102. In this study, we used human embryonic kidney 293 cells (HEK 293) to express SAP102. SAP102 palmitoylation was assayed using acyl-biotinyl exchange (ABE) method. The basal palmitoylation level of SAP102 and how the palmitoylation regulates SAP102 intracellular trafficking will provide a deeper understanding of SAP102 protein structure and how the protein plays a role at synpases

Production, Quality Control and Pharmacokinetic Studies of 166Ho-EDTMP for Therapeutic Applications

166Ho-EDTMP is a major therapeutic agent which is widely used in bone palliation therapy. In this study, a 166Ho-EDTMP complex was prepared successfully using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 ncm−2s−1) of natural Ho(NO3)3 samples (specific activity = 3–5 GBq/mg), dissolved in acidic media. The radiochemical purity of 166Ho-EDTMP was checked by ITLC (>99%) and stability studies in presence of human serum and final preparation were performed. The biodistribution of 166Ho-EDTMP and 166HoCl3 in wild-type rats was checked by scarification. SPECT imaging of 166Ho-EDTMP was also performed in wild-type rats. A comparative accumulation study for 166Ho-EDTMP and 166HoCl3 was performed for vital organs up to 48h. Significant bone accumulation (>70%) of the tracer in 48h was observed

Preparation and quality control of 177Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy

The 177Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (177Lu-PQ3) was prepared successfully with high radiochemical purity (> 99%). Lu-177 chloride was obtained by thermal neutron flux (4 × 1013 n.cm–2.s–1) of natural Lu2(NO3)3 sample, dissolved in acidic media. The radiochemical yield was checked by measuring the radiochemical purity of the 177Lu-PQ complex by ITLC (10 mM DTPA, pH = 5, as mobile phase). The final complex solution was injected intravenously into wild-type male rats and bio-distribution of the complex was checked for up to 48 hours. The dose limiting organs were shown to be the reticulu-endothelial system. The bio-distribution of the labelled compounds in tumour-bearing animals is under investigation. Nuclear Med Rev 2010; 13, 2: 49–5

Anti-cancer effect of Cissus quadrangularis on human glioblastoma cells

Objectives Glioblastoma multiforme (GBM) is a common and fatal brain tumour in the central nervous system with a poor survival rate and a median survival time of 15 months only. The standard treatment is aggressive surgical resection followed by radiotherapy and chemotherapy. However, effective drugs available in chemotherapy are limited. This study was designed to evaluate, for the first time, the potential therapeutic effect of Cissus quadrangularis (CQ) in human glioblastoma cells and to investigate its possible mechanisms of action. Methods In this study, we examined the anticancer activity of CQ in human glioblastoma U87 MG cells by cell viability assay, cell migration assay, immunofluorescence staining and Western blot. Results Our results demonstrated that CQ treatment induced U87 cytotoxicity, cell cycle arrest and cell death. The cytotoxicity of CQ mediates ER stress, autophagy and mitochondrial apoptosis by suppressing pro-survival signalling pathways (extracellular signal-regulated kinase and signal transducer and activator of transcription 3 pathways). Conclusions The findings of this study imply that CQ is a promising anti-cancer candidate for the treatment of GBM. Highlights The anticancer effect of Cissus quadrangularis (CQ) was studied in human glioblastoma U87 MG cells. It was demonstrated that CQ treatment induced cytotoxicity, cell cycle arrest and cell death in U87 MG cells. CQ may become a potential chemotherapy component for the treatment of glioblastoma multiforme

Optimal production and purification of n.c.a.143Pr as a promising palliative agent for the treatment of metastatic bone pain

Abstract This study proposes the beta-emitting radioisotope 143Pr as a promising candidate for palliative treatment of metastatic bone pain due to its desirable physical decay characteristics. An optimized process was developed for the production and purification of non-carrier-added 143Pr using a medium flux research reactor. Calculations were performed to determine the optimal irradiation time and cooling period for irradiating 1 mg of natural cerium oxide to indirectly produce 143Pr through the decay of 143Ce. Following irradiation and cooling, extraction chromatography was employed to efficiently isolate 143Pr from the irradiated target material. A column containing Ln-resin was used along with nitric acid as the mobile phase and an optional oxidation step with NaBrO3/ascorbic acid to separate 143Pr from impurities such as 143Ce and 141Ce. Radionuclidic purity of over 99.995% was achieved as confirmed through gamma spectroscopy, demonstrating effective separation of 143Pr. Additional quality control analyses established the chemical and radiochemical purity of the purified 143Pr nitrate product. With a half-life of 13.6 days and maximum beta energy of 0.937 MeV, 143Pr exhibits favorable properties for palliative bone pain therapy. This study therefore provides a viable method for producing high-purity 143Pr through the optimized irradiation and purification processes described. Further investigation is warranted to explore potential clinical applications of 143Pr for palliation of metastatic bone cancer pain

Synthesis and characterization of new ion-imprinted polymer for separation and preconcentration of uranyl (UO22+) ions

UO22+ ion-imprinted polymer materials used for solid-phase extraction were prepared by copolymerization of a ternary complex of uranyl ions with styrene and divinyl benzene in the presence of 2,2′-azobisisobutyronitrile. The imprinted particles were leached by HCl 6 M. Various parameters in polymerization steps such as DVB/STY ratio, time of polymerization and temperature of polymerization were varied to achieve the most efficient uranyl-imprinted polymer. X-ray diffraction (XRD), infra-red spectroscopy (IR), thermo gravimetric analysis (TGA), UV–vis and nitrogen sorption were used to characterize the polymer particles. The XRD results showed that uranyl ions were completely removed from the polymer after leaching process. IR Analysis indicated that the N,N′-ethylenebis(pyridoxylideneiminato) remained intact in the polymer even after leaching. Some parameters such as pH, weight of the polymer, elution time, eluent volume and aqueous phase volume which affects the efficiency of the polymer were studied

Radiosynthesis and evaluation of ytterbium-175 labeled bleomycin as therepeutic agent

ABSTRACT Introduction: Bleomycins are DNA-binding biomolecules, which can be used as targeted therapy carriers when labeled with particle-emitters such as Yb-175. In this work the development of Yb-175 bleomycin

Development of 166Ho-zoledronate as a bone marrow ablative agent

In this study, production, quality control and biodistribution studies of 166Ho-zoledronate have been presented as a possible bone marrow ablative agent. Ho-166 chloride was produced by thermal neutron irradiation of natural 165Ho(NO3)3 samples. 166Ho-zoledronate complex was prepared by adding the desired amount of zoledronate solution (0.2 mL, 150 mg/ml in 1 M NaOH) to appropriate amount of the 166HoCl3 solution.  Radiochemical purity of the complex was monitored by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. The biodistribution of 166Ho-zoledronate and 166HoCl3 in wild-type mice was checked up to 72 h. 166Ho-zoledronate complex was prepared in high radiochemical purity (> 99%, ITLC) and specific activity of 4.4 GBq/mmol. The major accumulation of radiolabelled complex was observed in the bone tissue. These findings suggest 166Ho-zoledronatehas can be a possible candidate for bone marrow ablation in patients with multiple myeloma