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Tinchou Li, Mingcheng Lee, Fuming Tsai, Yunhsiang Chen, Yiyin Lin, Maoliang Chen
BACKGROUND: Based on accumulating evidence, the regulation of protein expression by antipsychotic drugs (APDs) might be closely related to the control of psychotic symptoms when these drugs are used to treat mental disorders. The low quantity of nuclear proteins in the cell hinders their detection because signal for rare proteins are masked in most proteomic detection systems. METHODS: Nuclear proteins fractionated from APD-treated B35 cells were labeled with iTRAQ and detected by LC/MS/MS to investigate APD-induced alterations in nuclear protein expression...
March 7, 2018: BMC Pharmacology & Toxicology
Jiang Zou, Nian Wang, Manting Liu, Yongping Bai, Hao Wang, Ke Liu, Huali Zhang, Xianzhong Xiao, Kangkai Wang
Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro-angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro-angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively, each morning and evening for 2 weeks...
March 7, 2018: Journal of Cellular and Molecular Medicine
Annely Lorents, Pille Säälik, Ulo Langel, Margus Pooga
Proficient transport vectors called cell-penetrating peptides (CPPs) internalize into eukaryotic cells mostly via endocytic pathways and facilitate the uptake of various cargo molecules attached to them. However, some CPPs are able to induce disturbances in the plasma membrane and translocate through it seemingly in energy-independent manner. For understanding this phenomenon, giant plasma membrane vesicles (GPMVs) derived from the cells is a beneficial model system, since GPMVs have a complex membrane composition comparable to the cells, yet lack cellular energy-dependent mechanisms...
March 6, 2018: Bioconjugate Chemistry
Preethi Devanand, Yukiko Oya, Santhoshkumar Sundaramoorthy, Kye Yong Song, Tatsuro Watanabe, Yasuhito Kobayashi, Yoshihiko Shimizu, Soon Auck Hong, Masami Suganuma, In Kyoung Lim
To understand the regulation of Helicobacter pylori (H. pylori)-associated gastric carcinogenesis, we examined the effect of B-cell translocation gene 2 (BTG2) expression on the biological activity of Tipα, an oncoprotein secreted from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2/TIS21 ), has been reported to be a primary response gene that is transiently expressed in response to various stimulations. Here, we report that BTG2 is constitutively expressed in the mucous epithelium and parietal cells of the gastric gland in the stomach...
February 23, 2018: Experimental & Molecular Medicine
Wei-Hai Chen, Sohn Yang Sung, Michael Fadeev, Alessandro Cecconello, Rachel Nechushtai, Itamar Willner
Amino-triphenyl dicarboxylate-bridged Zr4+ metal-organic framework nanoparticles (NMOFs), 100-130 nm, are modified with a nucleic acid complementary to the VEGF aptamer. The nucleic acid-functionalized NMOFs were loaded with the anti-cancer drug doxorubicin (or Rhodamine 6G as a drug model), and the loaded NMOFs were capped by hybridization with the VEGF aptamer that yielded VEGF-responsive duplex nucleic acid gates. In the presence of VEGF, a biomarker over-expressed in cancer cells, selective unlocking of the gates proceeds through the formation of VEGF/aptamer complexes, resulting in the release of the loads...
February 21, 2018: Nanoscale
Iva Ugrinova, Maria Petrova, Mounira Chalabi-Dchar, Philippe Bouvet
Discovered in 1973, nucleolin is one of the most abundant phosphoproteins of the nucleolus. The ability of nucleolin to be involved in many cellular processes is probably related to its structural organization and its capability to form many different interactions with other proteins. Many functions of nucleolin affect cellular processes involved in oncogenesis-for instance: in ribosome biogenesis; in DNA repair, remodeling, and genome stability; in cell division and cell survival; in chemokine and growth factor signaling pathways; in angiogenesis and lymphangiogenesis; in epithelial-mesenchymal transition; and in stemness...
2018: Advances in Protein Chemistry and Structural Biology
Kei Daizumoto, Tetsuro Yoshimaru, Yosuke Matsushita, Tomoya Fukawa, Hisaori Uehara, Masaya Ono, Masato Komatsu, Hiro-Omi Kanayama, Toyomasa Katagiri
The p53 and EGFR pathways are frequently altered in bladder cancers, yet their contributions to its progression remain elusive. Here we report that DEAD box polypeptide 31 (DDX31) plays a critical role in the multistep progression of muscle invasive bladder cancer (MIBC) through its sequential interactions with mutant p53 (mutp53) and EGFR. In early MIBC cells, nuclear DDX31 bound mutp53/SP1 and enhanced mutp53 transcriptional activation, leading to migration and invasion of MIBC. Cytoplasmic DDX31 also bound EGFR and phospho-nucleolin (p-NCL) in advanced MIBC, leading to EGFR-Akt signaling activation...
February 13, 2018: Cancer Research
Suping Li, Qiao Jiang, Shaoli Liu, Yinlong Zhang, Yanhua Tian, Chen Song, Jing Wang, Yiguo Zou, Gregory J Anderson, Jing-Yan Han, Yung Chang, Yan Liu, Chen Zhang, Liang Chen, Guangbiao Zhou, Guangjun Nie, Hao Yan, Baoquan Ding, Yuliang Zhao
Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot...
March 2018: Nature Biotechnology
Xiaoling Yuan, Tao Hu, Hanwen He, Huan Qiu, Xuan Wu, Jingxian Chen, Minmin Wang, Cheng Chen, Shenghai Huang
BACKGROUND: Respiratory syncytial virus (RSV) infects the central nervous system, resulting in neurological symptoms. However, the precise underlying pathogenic mechanisms have not been elucidated. In the present study, the infectivity of RSV on N2a neuronal cells and the possible roles of Toll-like receptor 4 (TLR4) and nucleolin (C23) during RSV infection were investigated. METHODS: We compared two experimental groups (infected and non-infected) and monitored the RSV viral titers in the culture supernatant by a viral plaque assay...
February 10, 2018: Journal of Biomedical Science
Xiao-Ping Huang, Xiao Wang, Xiao-Lan Xie, Gao-Ping Zhang, Feng-Jiao Lv, Wen-Ting Weng, Fei Qiu, Zhao-Fa Li, Jun-Sheng Lin, Yong Diao
Kallistatin is a unique serine proteinase inhibitor and heparin-binding protein. A previous study conducted by our group indicated that kallistatin has antiangiogenic and antitumoral activities. In the present study, we report that kallistatin specifically binds to membrane surface-expressed nucleolin with high affinity. Antibody-mediated neutralization or siRNA-induced nucleolin knockdown results in loss of kallistatin suppression of endothelial cell proliferation and migration in vitro and tumor angiogenesis and growth in vivo...
January 5, 2018: Oncotarget
Michael Keck, Roelof Maarten van Dijk, Cornelia A Deeg, Katharina Kistler, Andreas Walker, Eva-Lotta von Rüden, Vera Russmann, Stefanie M Hauck, Heidrun Potschka
Information about epileptogenesis-associated changes in protein expression patterns is of particular interest for future selection of target and biomarker candidates. Bioinformatic analysis of proteomic data sets can increase our knowledge about molecular alterations characterizing the different phases of epilepsy development following an initial epileptogenic insult. Here, we report findings from a focused analysis of proteomic data obtained for the hippocampus and parahippocampal cortex samples collected during the early post-insult phase, latency phase, and chronic phase of a rat model of epileptogenesis...
April 2018: Neurobiology of Disease
Fang Cheng, Lars-Åke Fransson, Katrin Mani
Import of the polyamine spermine from the extracellular environment depends on the presence of cell surface heparan sulfate proteoglycans, such as glypican-1. This proteoglycan is internalized by endocytosis, releases its heparan sulfate chains in endosomes by a nitric oxide-, copper- and amyloid precursor protein-dependent mechanism, then penetrates the membrane and is transported to the nucleus and then to autophagosomes. This process is spontaneous or induced by ascorbate depending on the growth-state of the cell...
February 2, 2018: Experimental Cell Research
Qing-Lan Lyu, Bi-Mei Jiang, Bin Zhou, Li Sun, Zhong-Yi Tong, Yuan-Bin Li, Yu-Ting Tang, Hui Sun, Mei-Dong Liu, Xian-Zhong Xiao
BACKGROUND: Nucleolin (NCL) is the most abundant RNA-binding protein in the cell nucleolus and plays an important role in chromatin stability, ribosome assembly, ribosomal RNA maturation, ribosomal DNA transcription, nucleocytoplasmic transport, and regulation of RNA stability and translation efficiency. In addition to its anti-apoptotic properties, the underlying mechanisms associated with NCL-related roles in different cellular processes remain unclear. In this study, the effect of NCL on microRNA (miRNA) expression was evaluated by generating transgenic mice with myocardial overexpression of NCL and by analyzing microarrays of mature and precursor miRNAs from mice...
February 5, 2018: Chinese Medical Journal
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
Laura Terzaghi, Alberto Maria Luciano, Priscila C Dall Acqua, Silvia Modina, John J Peluso, Valentina Lodde
Progesterone Receptor Membrane Component-1 (PGRMC1) is a highly conserved multifunctional protein that is found in numerous systems, including reproductive system. Interestingly, PGRMC1 is expressed at several intracellular locations, including the nucleolus. The aim of this study is to investigate the functional relationship between PGRMC1 and nucleolus. Immunofluorescence experiments confirmed PGRMC1's nucleolar localization in cultured bovine granulosa cells (bGC) and oocytes. Additional experiments conducted on bGC revealed that PGRMC1 co-localizes with nucleolin (NCL), a major nucleolar protein...
January 16, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Youlin Tuo, Ning An, Ming Zhang
The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of P<0.05. Based on the protein‑protein interactions (PPIs) in the Biological General Repository for Interaction Datasets, Human Protein Reference Database and Biomolecular Interaction Network Database, the PPI network of the feature genes was constructed...
January 9, 2018: Molecular Medicine Reports
Markus M Luedi, Sanjay K Singh, Jennifer C Mosley, Islam S A Hassan, Masumeh Hatami, Joy Gumin, Lukas Andereggen, Erik P Sulman, Frederick F Lang, Frank Stueber, Gregory N Fuller, Rivka R Colen, Pascal O Zinn
OBJECTIVE Dexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug's impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug's impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort...
January 12, 2018: Journal of Neurosurgery
Seyed Hossein Rajabnejad, Ahad Mokhtarzadeh, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani, Bibi Marjan Razavi
Melittin, a small water-soluble cationic amphipathic α-helical linear peptide, consisted of 26 amino acids, is the honeybee venom major constituent. Several reports have proved the lytic and apoptotic effects of melittin in several cancerous cell lines. In this study, we aimed to fabricate an AS1411 aptamer-melittin to specifically deliver melittin to nucleolin positive cells (A549). Melittin was covalently attached to antinucleolin aptamer (AS1411) and its toxicity in A549 (Nucleolin positive) and L929 (Nucleolin negative) was studied using MTT and Annexin V flow cytometry methods...
January 12, 2018: Drug Development and Industrial Pharmacy
Xiaoting Liu, Lina Wu, Lei Wang, Wei Jiang
To enhance efficacy of chemotherapy and achieve real-time imaging of cancer cells, it is crucial to develop nanocarriers with targeted drug delivery capacity and fluorescence property for cancer theranostics. Herein, a dual-targeting DNA tetrahedron nanocarrier (MUC1-Td-AS1411) was constructed for breast cancer cell imaging and targeted drug delivery. This nanocarrier consisted of three components: (i) DNA tetrahedron core for multivalent conjugation of function ligands and loading doxorubicin (Dox); (ii) activatable MUC1 aptamer probe (MUC1-probe), formed by the hybridization of MUC1 aptamer sequence with fluorophore extended from one vertex and complementary sequence with quencher, for targeting and imaging MUC1 protein on cytomembrane; (iii) AS1411 aptamer, which was hybridized to the overhang on three vertexes via prolonged sequence, for binding to nucleolin...
March 1, 2018: Talanta
Qian Zhang, Zhefan Stephen Chen, Ying An, Haizhen Liu, Yonghui Hou, Wen Li, Kwok-Fai Lau, Alex Koon, Jacky Ngo, Edwin Chan
Polyglutamine (polyQ) diseases are a set of progressive neurodegenerative disorders ascribed by the expression of both expanded CAG RNA and misfolded polyQ protein. We previously reported that the direct interaction between expanded CAG RNA and nucleolar protein nucleolin (NCL) leads to impediment of pre-ribosomal RNA (pre-rRNA) transcription, and eventually triggers nucleolar stress-induced apoptosis in polyQ diseases. Here, we report a 21-amino acid peptide, named beta-structured inhibitor for neurodegenerative disease (BIND), effectively suppresses expanded CAG RNA toxicity...
January 2, 2018: RNA
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