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https://www.readbyqxmd.com/read/28806787/antagonism-of-proteasome-inhibitor-induced-heme-oxygenase-1-expression-by-pink1-mutation
#1
Xiang-Jun Sheng, Hunag-Ju Tu, Wei-Lin Chien, Kai-Hsiang Kang, Dai-Hua Lu, Horng-Huei Liou, Ming-Jen Lee, Wen-Mei Fu
PTEN-induced putative kinase 1 (PINK1) is an integral protein in the mitochondrial membrane and maintains mitochondrial fidelity. Pathogenic mutations in PINK1 have been identified as a cause of early-onset autosomal recessive familial Parkinson's disease (PD). The ubiquitin proteasome pathway is associated with neurodegenerative diseases. In this study, we investigated whether mutations of PINK1 affects the cellular stress response following proteasome inhibition. Administration of MG132, a peptide aldehyde proteasome inhibitor, significantly increased the expression of heme oxygenase-1 (HO-1) in rat dopaminergic neurons in the substantia nigra and in the SH-SY5Y neuronal cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#2
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806752/the-escrt-iii-pathway-facilitates-cardiomyocyte-release-of-cbin1-containing-microparticles
#3
Bing Xu, Ying Fu, Yan Liu, Sosse Agvanian, Robert C Wirka, Rachel Baum, Kang Zhou, Robin M Shaw, TingTing Hong
Microparticles (MPs) are cell-cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold- generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus...
August 14, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#4
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#5
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28806729/erk2-and-jnk1-contribute-to-tnf-%C3%AE-induced-il-8-expression-in-synovial-fibroblasts
#6
Shinichi Namba, Rei Nakano, Taku Kitanaka, Nanako Kitanaka, Tomohiro Nakayama, Hiroshi Sugiya
Tumor necrosis factor α (TNF-α) induces the expression and secretion of interleukin 8 (IL-8), which contributes to synovitis in rheumatoid arthritis (RA). To elucidate the mechanism of the onset of RA, we used synovial fibroblasts without autoimmune inflammatory diseases and investigated MAPK signaling pathways in TNF-α-induced IL-8 expression. Synovial fibroblasts isolated from healthy dogs were characterized by flow cytometry, which were positive for the fibroblast markers CD29, CD44, and CD90 but negative for the hematopoietic cell markers CD14, CD34, CD45, and HLA-DR...
2017: PloS One
https://www.readbyqxmd.com/read/28806703/nox4-mediated-ros-production-induces-apoptotic-cell-death-via-down-regulation-of-c-flip-and-mcl-1-expression-in-combined-treatment-with-thioridazine-and-curcumin
#7
Seung Un Seo, Tae Hwan Kim, Dong Eun Kim, Kyoung-Jin Min, Taeg Kyu Kwon
Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA...
August 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/28806702/hmgb1-redox-during-sepsis
#8
Wasan Abdulmahdi, Devika Patel, May M Rabadi, Tala Azar, Edson Jules, Mark Lipphardt, Rameen Hashemiyoon, Brian B Ratliff
During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis...
August 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28806603/cancer-vaccines-in-the-era-of-checkpoint-blockade-the-magic-is-in-the-adjuvant
#9
REVIEW
Willem W Overwijk
While T cell checkpoint blockade therapy of various cancers yields impressive clinical benefits, most patients are not cured. This is thought to result from insufficient spontaneous tumor-specific T cell responses, a situation that could be remedied with cancer-specific vaccination. Much work is underway to identify cancer-specific antigens, leaving open the question of how to formulate these antigens in a manner that provokes potent cancer-specific T cell responses. In this review I discuss paradigms guiding adjuvant development, and consider what may constitutes a clinically relevant T cell response...
August 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28806595/advances-in-stem-cell-proteomics
#10
REVIEW
Nade Abazova, Jeroen Krijgsveld
Stem cells are at the basis of organismal development, characterized by their potential to differentiate towards specific lineages upon receiving proper signals. To understand the molecular principles underlying gain and loss of pluripotency, proteomics plays an increasingly important role owing to technical developments in mass spectrometry and implementation of innovative biochemical approaches. Here we review how quantitative proteomics has been used to investigate protein expression, localization, interaction and modification in stem cells both in vitro and in vivo, thereby complementing other omics approaches to study fundamental properties of stem cell plasticity...
August 11, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28806594/signaling-networks-in-the-control-of-pluripotency
#11
REVIEW
Hanzhi Zhao, Ying Jin
Embryonic stem cells (ESCs) are characterized by their ability of unlimited self-renewal in vitro and pluripotent developmental potential, which endows them with great values in basic research and future clinical application. However, realization of full potential of ESCs is dependent on the elucidation of molecular mechanisms governing ESCs, among which signaling pathways play critical roles. A great deal of efforts has been made in the past decades to understand what and how signaling pathways contribute to the establishment and maintenance of pluripotency...
August 11, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28806534/knockdown-of-snail-inhibits-epithelial-mesenchymal-transition-of-human-laryngeal-squamous-cell-carcinoma-hep-2-cells-through-vdr-signaling-pathway
#12
Xue Zhao, Dan Yu, Jingpu Yang, Kai Xue, Yan Liu, Chunshun Jin
It has been well-documented that Snail plays a decisive role in various tumors. However, the direct effect of Snail on laryngeal squamous cell carcinoma (LSCC) has not been elaborated. In this study, we firstly detected the expression of Snail in 14 samples of patients with LSCC and found that its content was high in cancer tissues compared with adjacent tissues. Then we established LSCC Hep-2 cells with Snail silencing and validated the knockdown efficiency by western blotting and real-time PCR. Results showed that silencing of Snail significantly inhibited the ability of adhesion, migration, and invasion of Hep-2 cells...
August 14, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28806507/triboelectric-nanogenerator-enabled-body-sensor-network-for-self-powered-human-heart-rate-monitoring
#13
Zhiming Lin, Jun Chen, Xiaoshi Li, Zhihao Zhou, Keyu Meng, Wei Wei, Jin Yang, Zhong Lin Wang
Heart rate monitoring plays a critical role in personal healthcare management. A low-cost, non-invasive and user-friendly heart rate monitoring system is highly desirable. Here, a self-powered wireless Body Sensor Network (BSN) system is developed for heart rate monitoring via integration of a downy-structure based triboelectric nanogenerator (D-TENG), a power management circuit, a heart rate sensor, a signal processing unit and Bluetooth module for wireless data transmission. By converting the inertia energy of human walking into electric power, a maximum power of 2...
August 14, 2017: ACS Nano
https://www.readbyqxmd.com/read/28806446/sema3a-reduces-sprouting-of-adult-rod-photoreceptors-in-vitro
#14
Frank Kung, Weiwei Wang, Tracy S Tran, Ellen Townes-Anderson
Purpose: Rod photoreceptor terminals respond to retinal injury with retraction and sprouting. Since the guidance cue Semaphorin3A (Sema3A) is observed in the retina after injury, we asked whether Sema3A contributes to structural plasticity in rod photoreceptors. Methods: We used Western blots and alkaline phosphatase (AP)-tagged neuropilin-1 (NPN-1) to detect the expression of Sema3A in an organotypic model of porcine retinal detachment. We then examined Sema3A binding to cultured salamander rod photoreceptors using AP-tagged Sema3A...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28806414/alpha-tocopherol-attenuates-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-npm-alk
#15
Yuki Uchihara, Fumihito Ueda, Kenji Tago, Yosuke Nakazawa, Tomoyuki Ohe, Tadahiko Mashino, Shigenobu Yokota, Tadashi Kasahara, Hiroomi Tamura, Megumi Funakoshi-Tago
Anaplastic large cell lymphomas (ALCL) are mainly characterized by harboring the fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3). We found that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties...
2017: PloS One
https://www.readbyqxmd.com/read/28806404/rig-i-and-il-6-are-negative-feedback-regulators-of-sting-induced-by-double-stranded-dna
#16
Xueling Wu, Jun Yang, Tao Na, Kehua Zhang, Andrew M Davidoff, Bao-Zhu Yuan, Youchun Wang
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA)...
2017: PloS One
https://www.readbyqxmd.com/read/28806395/rad6-promotes-dna-repair-and-stem-cell-signaling-in-ovarian-cancer-and-is-a-promising-therapeutic-target-to-prevent-and-treat-acquired-chemoresistance
#17
R R Somasagara, S M Spencer, K Tripathi, D W Clark, C Mani, L Madeira da Silva, J Scalici, H Kothayer, A D Westwell, R P Rocconi, K Palle
Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806136/harnessing-olig2-function-in-tumorigenicity-and-plasticity-to-target-malignant-gliomas
#18
Jennifer Kosty, Fanghui Lu, Robert Kupp, Shwetal Mehta, Q Richard Lu
Glioblastoma (GBM) is the most prevalent and malignant brain tumor, displaying notorious resistance to conventional therapy, partially due to molecular and genetic heterogeneity. Understanding the mechanisms for gliomagenesis, tumor stem/progenitor cell propagation and phenotypic diversity is critical for devising effective and targeted therapy for this lethal disease. The basic helix-loop-helix transcription factor OLIG2, which is universally expressed in gliomas, has emerged as an important player in GBM cell reprogramming, genotoxic resistance, and tumor phenotype plasticity...
August 14, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28806133/autophagy-dictates-metabolism-and-differentiation-of-inflammatory-immune-cells
#19
Thomas Riffelmacher, Felix Clemens Richter, Anna Katharina Simon
The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. Particularly, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate. One of the proposed mechanisms is the impact of autophagy on the altered metabolic states during immune cell differentiation...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28806053/de-blurring-signal-network-dynamics
#20
Dominic Kamps, Leif Dehmelt
To orchestrate the function and development of multicellular organisms, cells integrate intra- and extracellular information. This information is processed via signal networks in space and time, steering dynamic changes in cellular structure and function. Defects in those signal networks can lead to developmental disorders or cancer. However, experimental analysis of signal networks is challenging as their state changes dynamically and differs between individual cells. Thus, causal relationships between network components are blurred if lysates from large cell populations are analyzed...
August 14, 2017: ACS Chemical Biology
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