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ribosome inactivating protein

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https://www.readbyqxmd.com/read/28932186/da-negatively-regulates-igf-i-actions-implicated-in-cognitive-function-via-interaction-of-psd95-and-nnos-in-minimal-hepatic-encephalopathy
#1
Saidan Ding, Weishan Zhuge, Xuebao Wang, Jianjing Yang, Yuanshao Lin, Chengde Wang, Jiangnan Hu, Qichuan Zhuge
Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28928861/down-regulation-of-rps9-inhibits-osteosarcoma-cell-growth-through-inactivation-of-mapk-signaling-pathway
#2
Dong-Dong Cheng, Bin Zhu, Shi-Jie Li, Ting Yuan, Qing-Cheng Yang, Cun-Yi Fan
Objectives: Osteosarcoma is the most common malignant bone tumor in adolescents; however, the mechanisms involved in the pathogenesis and progression of osteosarcoma remain to be elucidated. Researchers have provided valuable insights into the tumorigenesis of Ribosomal protein S9 (RPS9) in some cancers. The purpose of this study was to elucidate the expression, functions, and mechanisms of RPS9 in human osteosarcoma. Methods: The expression of RPS9 in osteosarcoma tissues and cell lines was evaluated by qRT-PCR and western blotting...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28919908/hepatic-s6k1-partially-regulates-lifespan-of-mice-with-mitochondrial-complex-i-deficiency
#3
Takashi K Ito, Chenhao Lu, Jacob Khan, Quy Nguyen, Heather Z Huang, Dayae Kim, James Phillips, Jo Tan, Yenna Lee, Tuyet Nguyen, Samy Khessib, Natalie Lim, Surapat Mekvanich, Joshua Oh, Victor V Pineda, Weirong Wang, Alessandro Bitto, Jonathan Y An, John F Morton, Mitsutoshi Setou, Warren C Ladiges, Matt Kaeberlein
The inactivation of ribosomal protein S6 kinase 1 (S6K1) recapitulates aspects of caloric restriction and mTORC1 inhibition to achieve prolonged longevity in invertebrate and mouse models. In addition to delaying normative aging, inhibition of mTORC1 extends the shortened lifespan of yeast, fly, and mouse models with severe mitochondrial disease. Here we tested whether disruption of S6K1 can recapitulate the beneficial effects of mTORC1 inhibition in the Ndufs4 knockout (NKO) mouse model of Leigh Syndrome caused by Complex I deficiency...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28912890/glioma-dual-targeting-nanohybrid-protein-toxin-constructed-by-intein-mediated-site-specific-ligation-for-multistage-booster-delivery
#4
Yingzhi Chen, Meng Zhang, Hongyue Jin, Dongdong Li, Fan Xu, Aihua Wu, Jinyu Wang, Yongzhuo Huang
Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences...
2017: Theranostics
https://www.readbyqxmd.com/read/28911628/antifungal-activity-of-momordica-charantia-seed-extracts-toward-the-pathogenic-fungus-fusarium-solani-l
#5
Shuzhen Wang, Yongliang Zheng, Fu Xiang, Shiming Li, Guliang Yang
Momordica charantia L., a vegetable crop with high nutritional value, has been used as an antimutagenic, antihelminthic, anticancer, antifertility, and antidiabetic agent in traditional folk medicine. In this study, the antifungal activity of M. charantia seed extract toward Fusarium solani L. was evaluated. Results showed that M. charantia seed extract effectively inhibited the mycelial growth of F. solani, with a 50% inhibitory rate (IC50) value of 108.934 μg/mL. Further analysis with optical microscopy and fluorescence microscopy revealed that the seed extract led to deformation of cells with irregular budding, loss of integrity of cell wall, as well as disruption of the fungal cell membrane...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904868/high-density-lipoprotein-protects-cardiomyocytes-from-oxidative-stress-via-the-pi3k-mtor-signaling-pathway
#6
Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Hideto Nakajima, Toshihiko Oshita, Shigeyasu Tsuda, Tetsuya Hara, Masakazu Shinohara, Tatsuro Ishida, Ken-Ichi Hirata
Low levels of plasma high-density lipoprotein (HDL) cholesterol are associated with an increased risk of heart failure, regardless of the presence or absence of coronary artery disease. However, the direct effects of HDL on failing myocardium have not been fully elucidated. We found that HDL treatment resulted in improved cell viability in H9c2 cardiomyocytes under oxidative stress. This cardioprotective effect of HDL was regulated via the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28900896/fusion-of-gelonin-and-anti-insulin-like-growth-factor-1-receptor-igf-1r-affibody-for-enhanced-brain-cancer-therapy
#7
Songhee Ham, Kyoung Ah Min, Jae Wook Yang, Meong Cheol Shin
Owing to the extraordinary potency in inhibiting protein translation that could eventually lead to apoptosis of tumor cells, ribosome-inactivating proteins (RIPs) such as gelonin have been considered attractive drug candidates for cancer therapy. However, due to several critical obstacles (e.g., severe toxicity issues caused by a lack of selectivity in their mode of action and the low cytotoxicity via poor cellular uptake, etc.), clinical application of RIPs is yet far from being accomplished. To overcome these challenges, in the present study, we engineered gelonin fusion proteins with anti-insulin-like growth factor-1 receptor (IGF-1R) affibody ("IAFF") via the genetic recombinant method and the SpyCatcher/SpyTag-mediated conjugation method...
September 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28880866/ribosomal-dna-copy-number-amplification-and-loss-in-human-cancers-is-linked-to-tumor-genetic-context-nucleolus-activity-and-proliferation
#8
Meng Wang, Bernardo Lemos
Ribosomal RNAs (rRNAs) are transcribed from two multicopy DNA arrays: the 5S ribosomal DNA (rDNA) array residing in a single human autosome and the 45S rDNA array residing in five human autosomes. The arrays are among the most variable segments of the genome, exhibit concerted copy number variation (cCNV), encode essential components of the ribosome, and modulate global gene expression. Here we combined whole genome data from >700 tumors and paired normal tissues to provide a portrait of rDNA variation in human tissues and cancers of diverse mutational signatures, including stomach and lung adenocarcinomas, ovarian cancers, and others of the TCGA panel...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28835357/activation-of-%C3%AE-2-ampk-suppresses-ribosome-biogenesis-and-protects-against-myocardial-ischemia-reperfusion-injury
#9
Yang Cao, Naveen Bojjireddy, Maengjo Kim, Tao Li, Peiyong Zhai, Narayani Nagarajan, Junichi Sadoshima, Richard D Palmiter, Rong Tian
Rationale: AMP-activated protein kinase (AMPK) is a heterotrimeric protein that plays an important role in energy homeostasis and cardioprotection. Two isoforms of each subunit are expressed in the heart but the isoform-specific function of AMPK remains unclear. Objective: We sought to determine the role of γ2-AMPK in cardiac stress response using bioengineered cell lines and mouse models containing either isoform of the γ-subunit in the heart. Methods and Results: We found that γ2 but not γ1 or γ3 subunit translocated into nucleus upon AMPK activation...
August 23, 2017: Circulation Research
https://www.readbyqxmd.com/read/28831158/inhibition-of-post-transcriptional-steps-in-ribosome-biogenesis-confers-cytoprotection-against-chemotherapeutic-agents-in-a-p53-dependent-manner
#10
Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov
The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820908/ribosomopathy-like-properties-of-murine-and-human-cancers
#11
Sucheta Kulkarni, James M Dolezal, Huabo Wang, Laura Jackson, Jie Lu, Brian P Frodey, Atinuke Dosunmu-Ogunbi, Youjun Li, Marc Fromherz, Audry Kang, Lucas Santana-Santos, Panayiotis V Benos, Edward V Prochownik
Ribosomopathies comprise a heterogeneous group of hematologic and developmental disorders, often characterized by bone marrow failure, skeletal and other developmental abnormalities and cancer predisposition. They are associated with mutations and/or haplo-insufficiencies of ribosomal proteins (RPs) and inefficient ribosomal RNA (rRNA) processing. The resulting ribosomal stress induces the canonical p19ARF/Mdm2/p53 tumor suppressor pathway leading to proliferative arrest and/or apoptosis. It has been proposed that this pathway is then inactivated during subsequent neoplastic evolution...
2017: PloS One
https://www.readbyqxmd.com/read/28797946/genome-wide-screening-of-oryza-sativa-ssp-japonica-and-indica-reveals-a-complex-family-of-proteins-with-ribosome-inactivating-protein-domains
#12
Pieter Wytynck, Pierre Rougé, Els J M Van Damme
Ribosome-inactivating proteins (RIPs) are cytotoxic enzymes capable of halting protein synthesis by irreversible modification of ribosomes. Although RIPs are widespread they are not ubiquitous in the plant kingdom. The physiological importance of RIPs is not fully elucidated, but evidence suggests a role in the protection of the plant against biotic and abiotic stresses. Searches in the rice genome revealed a large and highly complex family of proteins with a RIP domain. A comparative analysis retrieved 38 RIP sequences from the genome sequence of Oryza sativa subspecies japonica and 34 sequences from the subspecies indica...
August 7, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28797563/binding-of-a-type-1-rip-and-of-its-chimeric-variant-to-phospholipid-bilayers-evidence-for-a-link-between-cytotoxicity-and-protein-membrane-interactions
#13
Elio Pizzo, Rosario Oliva, Rita Morra, Andrea Bosso, Sara Ragucci, Luigi Petraccone, Pompea Del Vecchio, Antimo Di Maro
Ribosome-inactivating proteins (RIPs) are enzymes, almost all identified in plants, able to kill cells by depurination of rRNAs. Recently, in order to improve resistance to proteolysis of a type 1 RIP (PD-L4), we produced a recombinant chimera combining it with a wheat protease inhibitor (WSCI). Resulting chimeric construct, named PD-L4UWSCI, in addition to present the functions of the two domains, shows also an enhanced cytotoxic action on murine cancer cells when compared to PD-L4. Since different ways of interaction of proteins with membranes imply different resulting effects on cells, in this study we investigate conformational stability of PD-L4 and PD-L4UWSCI and their interaction with membrane models (liposomes)...
August 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28768938/a-novel-molecular-model-of-plant-lectin-induced-programmed-cell-death-in-cancer
#14
Zheng Shi, Wen-Wen Li, Yong Tang, Li-Jia Cheng
Plant lectin, a class of highly diverse non-immune origin and carbohydrate-binding proteins, has been reported to specially induce cancer cell through programmed cell death (PCD) pathways (apoptosis and/or autophagy), shedding lights on screening promising anti-cancer candidate agent for further therapeutic trials. However, the complicated molecular mechanisms by which plant lectins induced the programmed death of tumor cells, have not yet been fully clarified. Here, we summarized a novel model, based on vast amount of research, by which plant lectins eliminate various types of cancer cells via three major pathways, including a) direct ribosome inactivating, b) endocytosis-dependent mitochondrial dysfunction and c) sugar-containing receptors binding...
August 1, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28755527/targeted-dianthin-is-a-powerful-toxin-to-treat-pancreatic-carcinoma-when-applied-in-combination-with-the-glycosylated-triterpene-so1861
#15
Cheenu Bhargava, Horst Dürkop, Xiangli Zhao, Alexander Weng, Matthias F Melzig, Hendrik Fuchs
Targeted cancer therapy provides the basis for the arrest of tumor growth in aggressive pancreatic carcinoma, however, a number of protein-based targeted toxins lack efficacy due to insufficient endosomal escape after being endocytosed. Therefore, we tested a fusion protein of the ribosome-inactivating protein dianthin and human epidermal growth factor in combination with a glycosylated triterpene (SO1861) that serves as an endosomal escape enhancer. In vitro investigations with the pancreatic carcinoma cell lines BxPC-3 and MIA PaCa-2 revealed no significant differences to off-target cells in the half maximal inhibitory concentration (IC50 ) for the fusion protein...
July 29, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28754944/cytosolic-antibody-delivery-by-lipid-sensitive-endosomolytic-peptide
#16
Misao Akishiba, Toshihide Takeuchi, Yoshimasa Kawaguchi, Kentarou Sakamoto, Hao-Hsin Yu, Ikuhiko Nakase, Tomoka Takatani-Nakase, Fatemeh Madani, Astrid Gräslund, Shiroh Futaki
One of the major obstacles in intracellular targeting using antibodies is their limited release from endosomes into the cytosol. Here we report an approach to deliver proteins, which include antibodies, into cells by using endosomolytic peptides derived from the cationic and membrane-lytic spider venom peptide M-lycotoxin. The delivery peptides were developed by introducing one or two glutamic acid residues into the hydrophobic face. One peptide with the substitution of leucine by glutamic acid (L17E) was shown to enable a marked cytosolic liberation of antibodies (immunoglobulins G (IgGs)) from endosomes...
August 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28750271/safety-tolerability%C3%A2-and-antitumour-activity-of-ly2780301-p70s6k-akt-inhibitor-in-combination-with-gemcitabine-in-molecularly-selected-patients-with-advanced-or-metastatic-cancer-a-phase-ib-dose-escalation-study
#17
MULTICENTER STUDY
Eric Angevin, Philippe A Cassier, Antoine Italiano, Anthony Gonçalves, Anas Gazzah, Catherine Terret, Maud Toulmonde, Gwenaëlle Gravis, Andrea Varga, Cédric Parlavecchio, Angelo Paci, Vianney Poinsignon, Jean-Charles Soria, Damien Drubay, Antoine Hollebecque
BACKGROUND: LY2780301, a dual inhibitor of protein kinase B (AKT) and the downstream effector p70 ribosomal protein S6 kinase (p70S6K), may inhibit progression in tumours relying on phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signalling pathway activation. This phase IB trial investigated the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetics (PK) and antitumour activity of LY2780301 plus gemcitabine in patients with advanced/metastatic solid tumours...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28741923/co-delivery-of-trichosanthin-and-albendazole-by-nano-self-assembly-for-overcoming-tumor-multidrug-resistance-and-metastasis
#18
Yisi Tang, Jianming Liang, Aihua Wu, Yingzhi Chen, Pengfei Zhao, Tingting Lin, Meng Zhang, Qin Xu, Jianxin Wang, Yongzhuo Huang
Multidrug resistance (MDR) and metastasis are the major obstacles in cancer chemotherapy. Nanotechnology-based combination therapy is a useful strategy. Recently, the combination of biologics and small drugs has attracted much attention in cancer therapy. Yet, the treatment outcomes are often compromised by the different pharmacokinetic profiles of the co-administered drugs thus leading to inconsistent drug uptake and suboptimal drug combination at the tumor sites. Nanotechnology-based co-delivery offers a promising method to address this problem, which is well demonstrated in the use of small drug combinations...
August 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28701787/avian-reovirus-p17-and-%C3%AF-a-act-cooperatively-to-downregulate-akt-by-suppressing-mtorc2-and-cdk2-cyclin-a2-and-upregulating-proteasome-psmb6
#19
Wei-Ru Huang, Pei-I Chi, Hung-Chuan Chiu, Jue-Liang Hsu, Brent L Nielsen, Tsai-Ling Liao, Hung-Jen Liu
Although we have shown that avian reovirus (ARV) p17-mediated inhibition of Akt leads to induction of autophagy, the precise mechanisms remain largely unknown. This study has identified a specific mechanism by which ARV coordinately regulates the degradation of ribosomal proteins by p17-mediated activation of E3 ligase MDM2 that targets ribosomal proteins and by σA-mediated upregulation of proteasome PSMB6. In addition to downregulating ribosomal proteins, p17 reduces mTORC2 assembly and disrupts mTORC2-robosome association, both of which inactivate mTORC2 leading to inhibition of Akt phosphorylation at S473...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693237/inhibitory-effects-of-delphinidin-on-the-proliferation-of-ovarian-cancer-cells-via-pi3k-akt-and-erk-1-2-mapk-signal-transduction
#20
Whasun Lim, Gwonhwa Song
Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical properties against various chronic diseases and types of cancer. However, little is known about its preventative effects on epithelial ovarian cancer, a disease that is associated with a low survival rate, a poor prognosis and a high rate of recurrence. The results of the present study demonstrated that the proliferation of SKOV3 cells decreased in a dose-dependent manner in response to treatment with delphinidin, and the phosphorylation of carcinogenic protein kinases associated with the progression of epithelial ovarian cancer was affected by delphinidin treatment...
July 2017: Oncology Letters
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