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https://www.readbyqxmd.com/read/29665004/thiostrepton-degrades-mutant-p53-by-eliciting-an-autophagic-response-in-sw480-cells
#1
Dhanya Kalathil, Manu Prasad, Maharrish Chelladurai, Samu John, Asha S Nair
Mutations in p53 gene are one of the hallmarks of tumor development. Specific targeting of mutant p53 protein has a promising role in cancer therapeutics. Our preliminary observation showed destabilization of mutant p53 protein in SW480, MiaPaCa and MDAMB231 cell lines upon thiostrepton treatment. In order to elucidate the mechanism of thiostrepton triggered mutant p53 degradation, we explored the impact of proteasome inhibition on activation of autophagy. Combined treatment of thiostrepton and cycloheximide/chloroquine prevented the degradation of mutant p53 protein, reinforcing autophagy as the means of mutant p53 destabilization...
April 17, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29578315/genes-involved-in-stress-response-influence-lithium-efficacy-in-bipolar-patients
#2
Aleksandra Szczepankiewicz, Beata Narozna, Janusz K Rybakowski, Sebastian Kliwicki, Piotr Czerski, Monika Dmitrzak-Węglarz, Maria Skibińska, Joanna Twarowska-Hauser, Joanna Pawlak
OBJECTIVES: In mood disorders, chronic stimulation with stress results in aberrant regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Lithium was shown to influence HPA axis function. The underlying genetic background as well as environmental context may influence the stress response, and therefore lithium efficacy. The aim of the present study was to analyze if genetic variants located in genes involved in HPA axis regulation affect the response to long-term lithium treatment in bipolar patients...
March 26, 2018: Bipolar Disorders
https://www.readbyqxmd.com/read/29452213/nanoemulsion-of-atovaquone-as-a-promising-approach-for-treatment-of-acute-and-chronic-toxoplasmosis
#3
Sanaz Jafarpour Azami, Amir Amani, Hossein Keshavarz, Roqya Najafi-Taher, Mehdi Mohebali, Mohammad Ali Faramarzi, Mahmood Mahmoudi, Saeedeh Shojaee
Treatment of toxoplasmosis is necessary in congenital form and immunocompromised patients. Atovaquone is a powerful suppressor of protozoan parasites with a broad-spectrum activity, but an extremely low water solubility and bioavailability. In this study, nanoemulsion of this drug was prepared with grape seed oil using spontaneous emulsification method to increase bioavailability and efficacy of atovaquone for treatment of toxoplasmosis. In vitro activity of atovaquone nanoemulsion against T. gondii, RH and Tehran strains, was assessed in HeLa cell culture...
February 13, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29348634/a-biosensor-based-framework-to-measure-latent-proteostasis-capacity
#4
Rebecca J Wood, Angelique R Ormsby, Mona Radwan, Dezerae Cox, Abhishek Sharma, Tobias Vöpel, Simon Ebbinghaus, Mikael Oliveberg, Gavin E Reid, Alex Dickson, Danny M Hatters
The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation. The biosensor system comprises a series of barnase kernels with differing folding stability that engage primarily with HSP70 and HSP90 family proteins...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316663/modulation-of-protein-quality-control-and-proteasome-to-autophagy-switch-in-immortalized-myoblasts-from-duchenne-muscular-dystrophy-patients
#5
Marion Wattin, Loïc Gaweda, Pascale Muller, Mathieu Baritaud, Charlotte Scholtes, Chloé Lozano, Kathrin Gieseler, Carole Kretz-Remy
The maintenance of proteome integrity is of primary importance in post-mitotic tissues such as muscle cells; thus, protein quality control mechanisms must be carefully regulated to ensure their optimal efficiency, a failure of these processes being associated with various muscular disorders. Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophies and is caused by mutations in the dystrophin gene. Protein quality control modulations have been diversely observed in degenerating muscles of patients suffering from DMD or in animal models of the disease...
January 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29189098/the-effects-of-ovarian-hormones-on-stressor-induced-hormonal-responses-glucocorticoid-receptor-expression-and-translocation-and-genes-related-to-receptor-signaling-in-adult-female-rats
#6
Matthew R Green, Marina L Marcolin, Cheryl M McCormick
Estradiol potentiates hypothalamic-pituitary-adrenal activity and delays the return of glucocorticoid secretion to baseline after a stressor exposure in female rats; we investigated whether estradiol effects involve actions on glucocorticoid receptor (GR) translocation and expression of receptor co-chaperones. In Experiment 1 intact females and ovariectomized (OVX) females were treated for four days with vehicle (VEH), 17β-estradiol benzoate (EB), or EB and progesterone (EB + P). Samples were taken from rats in the home cage (baseline) or after 30 min of restraint stress in a plastic restrainer (post-restraint) (n = 10/group)...
March 2018: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/29099775/whole-blood-mrna-expression-based-prognosis-of-metastatic-renal-cell-carcinoma
#7
Karthik V Giridhar, Carlos P Sosa, David W Hillman, Cristobal Sanhueza, Candace L Dalpiaz, Brian A Costello, Fernando J Quevedo, Henry C Pitot, Roxana S Dronca, Donna Ertz, John C Cheville, Krishna Vanaja Donkena, Manish Kohli
The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset...
November 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28680390/the-role-of-the-heat-shock-protein-b8-hspb8-in-motoneuron-diseases
#8
REVIEW
Paola Rusmini, Riccardo Cristofani, Mariarita Galbiati, Maria E Cicardi, Marco Meroni, Veronica Ferrari, Giulia Vezzoli, Barbara Tedesco, Elio Messi, Margherita Piccolella, Serena Carra, Valeria Crippa, Angelo Poletti
Amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA) are two motoneuron diseases (MNDs) characterized by aberrant protein behavior in affected cells. In familial ALS (fALS) and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which then accumulate in form of aggregates. Notably, some of these proteins accumulate into aggregates also in sporadic ALS (sALS) even if not mutated. To prevent proteotoxic stresses detrimental to cells, misfolded and/or aggregated proteins must be rapidly removed by the protein quality control (PQC) system...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28677535/generation-of-a-bag1-homozygous-knockout-mouse-embryonic-stem-cell-line-using-crispr-cas9
#9
Cheng-Cheng Tang, Li Pik Shan, Wu-Ming Wang, Gang Lu, Rahul S Tare, Kenneth Ka Ho Lee
Bag1 transcribes a multifunctional protein that participates in many important biological processes such as cell apoptosis, proliferation, differentiation and embryo development. Despite numerous published studies, the role of Bag1 in the context of embryonic stem (ES) cells, has not been explored. To investigate the function of Bag1 in ES cells, we generated mutant Bag1(-/-) ES cells using the CRISPR/Cas9 system. We established that the Bag1 double knockout ES cell line maintained their pluripotency, possessed a normal karyotype and the ability to differentiate into all three germ layers...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28439591/targeting-secondary-protein-complexes-in-drug-discovery-studying-the-druggability-and-chemical-biology-of-the-hsp70-bag1-complex
#10
Lindsay E Evans, Keith Jones, Matthew D Cheeseman
Proteins typically carry out their biological functions as multi-protein complexes, which can significantly affect the affinity of small-molecule inhibitors. HSP70 is an important target in oncology, so to study its chemical biology and the drug discovery potential of the HSP70/BAG1 complex, we designed a high-affinity non-nucleotide fluorescence polarisation probe.
May 4, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28424629/molecular-and-cellular-mechanisms-of-apoptosis-during-dissociated-spermatogenesis
#11
Tengfei Liu, Lingling Wang, Hong Chen, Yufei Huang, Ping Yang, Nisar Ahmed, Taozhi Wang, Yi Liu, Qiusheng Chen
Apoptosis is a tightly controlled process by which tissues eliminate unwanted cells. Spontaneous germ cell apoptosis in testis has been broadly investigated in mammals that have an associated spermatogenesis pattern. However, the mechanism of germ cell apoptosis in seasonally breeding reptiles following a dissociated spermatogenesis has remained enigmatic. In the present study, morphological evidence has clearly confirmed the dissociated spermatogenesis pattern in Pelodiscus sinensis. TUNEL and TEM analyses presented dynamic changes and ultrastructural characteristics of apoptotic germ cells during seasonal spermatogenesis, implying that apoptosis might be one of the key mechanisms to clear degraded germ cells...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28424560/an-exploratory-study-of-host-polymorphisms-in-genes-that-clinically-characterize-breast-cancer-tumors-and-pretreatment-cognitive-performance-in-breast-cancer-survivors
#12
Theresa A Koleck, Catherine M Bender, Beth Z Clark, Christopher M Ryan, Puja Ghotkar, Adam Brufsky, Priscilla F McAuliffe, Priya Rastogi, Susan M Sereika, Yvette P Conley
PURPOSE: Inspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28402699/inhibition-of-retrograde-transport-modulates-misfolded-protein-accumulation-and-clearance-in-motoneuron-diseases
#13
Riccardo Cristofani, Valeria Crippa, Paola Rusmini, Maria Elena Cicardi, Marco Meroni, Nausicaa V Licata, Gessica Sala, Elisa Giorgetti, Christopher Grunseich, Mariarita Galbiati, Margherita Piccolella, Elio Messi, Carlo Ferrarese, Serena Carra, Angelo Poletti
Motoneuron diseases, like spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS), are associated with proteins that because of gene mutation or peculiar structures, acquire aberrant (misfolded) conformations toxic to cells. To prevent misfolded protein toxicity, cells activate a protein quality control (PQC) system composed of chaperones and degradative pathways (proteasome and autophagy). Inefficient activation of the PQC system results in misfolded protein accumulation that ultimately leads to neuronal cell death, while efficient macroautophagy/autophagy-mediated degradation of aggregating proteins is beneficial...
August 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28358147/a-plant-bcl-2-associated-athanogene-is-proteolytically-activated-to-confer-fungal-resistance
#14
COMMENT
Mehdi Kabbage, Ryan Kessens, Martin B Dickman
The Bcl-2-associated athanogene (BAG) family is a multifunctional group of proteins involved in numerous cellular functions ranging from apoptosis to tumorigenesis. These proteins are evolutionarily conserved and encode a characteristic region known as the BAG domain. BAGs function as adapter proteins forming complexes with signaling molecules and molecular chaperones. In humans, a role for BAG proteins has been suggested in tumor growth, HIV infection, and neurodegenerative diseases; as a result, the BAGs are attractive targets for therapeutic interventions, and their expression in cells may serve as a predictive tool for disease development...
April 16, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28303856/effect-of-matrix-metallopeptidase-13-on-the-function-of-mouse-bone-marrow-derived-dendritic-cells
#15
Xiao-Dong Li, Xin-Rui Zhang, Zhi-Hao Li, Yang Yang, Duo Zhang, Heng Zheng, Shu-Ying Dong, Juan Chen, Xian-Dong Zeng
BACKGROUND: Dendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 (MMP-13), a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs). The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28266723/contribution-of-dopamine-neurotransmission-in-proconvulsant-effect-of-toxoplasma-gondii-infection-in-male-mice
#16
Jalal Babaie, Mohammad Sayyah, Pezhman Fard-Esfahani, Majid Golkar, Kourosh Gharagozli
Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One-third of world's population is infected with Toxoplasma gondii (T. gondii). This intracellular parasite has high tendency to excitable cells including neurons. We assessed seizure susceptibility and involvement of dopaminergic system in male mice with acute and chronic T. gondii infection. Mice were infected by intraperitoneal injection of T. gondii cysts. Acute and chronic stages of infection were determined by quantification of SAG1/BAG1 transcripts and level of repetitive REP-529 sequence in the brain of mice by real-time PCR...
March 7, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28251183/opposing-transcriptional-mechanisms-regulate-toxoplasma-development
#17
Dong-Pyo Hong, Joshua B Radke, Michael W White
The Toxoplasma biology that underlies human chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite stage. We investigated the roles of two alkaline-stress-induced ApiAP2 transcription factors, AP2IV-3 and AP2IX-9, in bradyzoite development. These factors were expressed in two overlapping waves during bradyzoite development, with AP2IX-9 increasing expression earlier than AP2IV-3, which peaked as AP2IX-9 expression was declining. Disruption of the AP2IX-9 gene enhanced, while deletion of AP2IV-3 gene decreased, tissue cyst formation, demonstrating that these factors have opposite functions in bradyzoite development...
January 2017: MSphere
https://www.readbyqxmd.com/read/28165652/candidate-susceptibility-variants-for-esophageal-squamous-cell-carcinoma
#18
Iikki Donner, Riku Katainen, Tomas Tanskanen, Eevi Kaasinen, Mervi Aavikko, Kristian Ovaska, Miia Artama, Eero Pukkala, Lauri A Aaltonen
Esophageal cancer is common worldwide, and often fatal. The major histological subtype is esophageal squamous cell carcinoma (ESCC). ESCC shows familial aggregation and high heritability. Mutations in RHBDF2 cause tylosis, a very rare disorder characterized by high life-time risk of ESCC, but no other well-established predisposition genes have been identified. To identify candidate susceptibility variants for ESCC we utilized the Population Information System and the Finnish cancer registry to find study materials by clustering ESCC patients by family name at birth and municipality at birth...
June 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27998983/bag1-co-chaperone-promotes-trc8-e3-ligase-dependent-degradation-of-misfolded-human-ether-a-go-go-related-gene-herg-potassium-channels
#19
Christine Hantouche, Brittany Williamson, William C Valinsky, Joshua Solomon, Alvin Shrier, Jason C Young
Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27682262/rare-copy-number-alterations-and-copy-neutral-loss-of-heterozygosity-revealed-in-ameloblastomas-by-high-density-whole-genome-microarray-analysis
#20
Marina Gonçalves Diniz, Alessandra Pires Duarte, Rolando A Villacis, Bruna V A Guimarães, Luiz Cláudio Pires Duarte, Sílvia R Rogatto, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes
BACKGROUND: Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors. METHODS: We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status...
September 28, 2016: Journal of Oral Pathology & Medicine
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