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FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology

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https://www.readbyqxmd.com/read/29301945/modulation-of-glutathione-promotes-apoptosis-in-triple-negative-breast-cancer-cells
#1
Tara Miran, Andreas T J Vogg, Natascha Drude, Felix M Mottaghy, Agnieszka Morgenroth
Triple-negative breast cancer has an extremely high rate of relapse. This is particularly due to the existence and survival of cancer stem cells (CSCs) characterized by increased amounts of glutathione (GSH). In this study, we evaluated the potential of pharmacological GSH depletion to sensitize CSCs to ionizing radiotherapy with an I-125-labeled nucleoside analog, 5-iodo-4'-thio-2'-deoxyuridine (ITdU). CSCs were isolated using CD24-- and CD44+-specific microbeads. GSH and reactive oxygen species (ROS) were evaluated by fluorescence-activated cell sorting...
January 4, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29301944/y-chromosome-lineage-determines-cardiovascular-organ-t-cell-infiltration-in-the-stroke-prone-spontaneously-hypertensive-rat
#2
Shanzana I Khan, Karen L Andrews, Kristy L Jackson, Basimah Memon, Ann-Maree Jefferis, Man K S Lee, Henry Diep, Zihui Wei, Grant R Drummond, Geoffrey A Head, Garry L Jennings, Andrew J Murphy, Antony Vinh, Amanda K Sampson, Jaye P F Chin-Dusting
The essential role of the Y chromosome in male sex determination has largely overshadowed the possibility that it may exert other biologic roles. Here, we show that Y-chromosome lineage is a strong determinant of perivascular and renal T-cell infiltration in the stroke-prone spontaneously hypertensive rat, which, in turn, may influence vascular function and blood pressure (BP). We also show, for the first time to our knowledge, that augmented perivascular T-cell levels can directly instigate vascular dysfunction, and that the production of reactive oxygen species that stimulate cyclo-oxygenase underlies this...
January 4, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29298863/dual-regulation-of-hmgb1-by-combined-jnk1-2-atf2-axis-with-mir-200-family-in-nonalcoholic-steatohepatitis-in-mice
#3
Xin Chen, Yan Ling, Yanping Wei, Jing Tang, Yibing Ren, Baohua Zhang, Feng Jiang, Hengyu Li, Ruoyu Wang, Wen Wen, Guishuai Lv, Mengchao Wu, Lei Chen, Liang Li, Hongyang Wang
In the context of diabetes, obesity, and metabolic syndrome, the inflammatory signaling has critical roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain poorly delineated. Herein, early and persistently elevated, proinflammatory cytokine HMGB1 expression was detected in a high-fat diet (HFD)-induced NAFLD model in C57BL/6 mice. The expression and extracellular release of HMGB1 was rapidly and dramatically induced by saturated palmitic acid in vitro HFD-induced inflammatory response and liver function impairment were both mitigated after the inhibition of endogenous HMGB1 by neutralizing antibody in vivo The up-regulation of HMGB1 was thought to be modified by dual channels: in the transcriptional level, it was regulated by JNK1/JNK2-ATF2 axis; post-transcriptionally, it was regulated by the microRNA (miR)-200 family, especially miR-429...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29298862/deregulation-of-hippo-taz-pathway-during-renal-injury-confers-a-fibrotic-maladaptive-phenotype
#4
Sandybell Anorga, Jessica M Overstreet, Lucas L Falke, Jiaqi Tang, Roel G Goldschmeding, Paul J Higgins, Rohan Samarakoon
Although yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), nuclear transducers of the Hippo pathway, are mostly silent in adult organs, aberrant activation of YAP/TAZ promotes tumorigenesis and abnormal tissue repair. The extent of involvement of TAZ in chronic kidney disease (CKD) is unknown. In our study, increased TAZ nuclear accumulation and expression in the tubulointerstitium was readily evident in 3 models of renal injury including obstructive, aristolochic acid (AA), and diabetic nephropathy, correlating with fibrosis progression...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29298861/hypersensitive-assessment-of-aryl-hydrocarbon-receptor-transcriptional-activity-using-a-novel-truncated-cyp1a-promoter-in-zebrafish
#5
Juan-Juan Luo, Dong-Sheng Su, Shao-Lin Xie, Yi Liu, Pei Liu, Xiao-Jun Yang, De-Sheng Pei
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant (POP), an unintentional byproduct of various industrial processes, and a human carcinogen. The expression of the cytochrome P450 1A (cyp1a) gene is upregulated in the presence of TCDD through activating the aryl hydrocarbon receptor pathway in a dose-dependent manner. Several essential response elements, including the 8 potential xenobiotic response elements in the cyp1a promoter region, have been identified to be the main functional parts for the response to TCDD...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295867/hexose-6-phosphate-dehydrogenase-controls-cancer-cell-proliferation-and-migration-through-pleiotropic-effects-on-the-unfolded-protein-response-calcium-homeostasis-and-redox-balance
#6
Maria Tsachaki, Natasa Mladenovic, Hana Štambergová, Julia Birk, Alex Odermatt
Hexose-6-phosphate dehydrogenase (H6PD) produces reduced NADPH in the endoplasmic reticulum (ER) lumen. NADPH constitutes a cofactor for many reducing enzymes, and its inability to traverse biologic membranes makes in situ synthesis of NADPH in the ER lumen indispensable. The H6PD gene is amplified in several types of malignancies, and earlier work pointed toward a potential involvement of the enzyme in cancer cell growth. In the present study, we demonstrated a pivotal role of H6PD in proliferation and migratory potential of 3 human breast cancer cell lines...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295866/connexin-43-gap-junctions-contribute-to-brain-endothelial-barrier-hyperpermeability-in-familial-cerebral-cavernous-malformations-type-iii-by-modulating-tight-junction-structure
#7
Allison M Johnson, James P Roach, Anna Hu, Svetlana M Stamatovic, Michal R Zochowski, Richard F Keep, Anuska V Andjelkovic
Familial cerebral cavernous malformations type III (fCCM3) is a disease of the cerebrovascular system caused by loss-of-function mutations in ccm3 that result in dilated capillary beds that are susceptible to hemorrhage. Before hemorrhage, fCCM3 lesions are characterized by a hyperpermeable blood-brain barrier (BBB), the key pathologic feature of fCCM3. We demonstrate that connexin 43 (Cx43), a gap junction (GJ) protein that is incorporated into the BBB junction complex, is up-regulated in lesions of a murine model of fCCM3...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295865/trans-binding-of-ufm1-to-uba5-stimulates-uba5-homodimerization-and-atp-binding
#8
Bayan Mashahreh, Fouad Hassouna, Nadine Soudah, Einav Cohen-Kfir, Roi Strulovich, Yoni Haitin, Reuven Wiener
All ubiquitin-like proteins (UBLs) undergo an activation process before their conjugation to target proteins. Although the steps required for the activation of UBLs are conserved and common to all UBLs, we have previously shown that the activation of the UBL, ubiquitin fold modifier 1 (UFM1) by the E1, Ufm1 modifier-activating enzyme 5 (UBA5) is executed in a trans-binding mechanism, not observed in any other E1. In this study, we explored the necessity of that mechanism for UFM1 activation and found that it is needed not only for UFM1 binding to UBA5 but also for stabilizing the UBA5 homodimer...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295864/harnessing-an-rna-mediated-chaperone-for-the-assembly-of-influenza-hemagglutinin-in-an-immunologically-relevant-conformation
#9
Seung Won Yang, Yo Han Jang, Soon Bin Kwon, Yoon Jae Lee, Wonil Chae, Young Ho Byun, Paul Kim, Chan Park, Young Jae Lee, Choon Kang Kim, Young Seok Kim, Seong Il Choi, Baik Lin Seong
A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins. The RNA as a molecular chaperone (chaperna) activity is intrinsic to some ribozymes and is operational during viral infections. Our purpose was to test whether influenza hemagglutinin (HA) can be assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity. An RNA-interacting domain (RID) from the host being immunized was selected as a docking tag for RNA binding, which served as a transducer for the chaperna function for de novo folding and trimeric assembly of RID-HA1...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295863/chicken-nanog-self-associates-via-a-novel-folding-upon-binding-mechanism
#10
Hee Jung Choi, Iktae Kim, Hong Jo Lee, Young Hyun Park, Jeong-Yong Suh, Jae Yong Han
NANOG plays a pivotal role in pluripotency acquisition and lineage specification in higher vertebrates, and its expression is restricted to primordial germ cells (PGCs) during early embryonic development. Mammalian NANOG self-associates via conserved tryptophan-repeat motifs in the C-terminal domain (CTD) to maintain pluripotency. Avian NANOG, however, lacks the conserved motifs, and the molecular mechanism underlying the biologic function is not clearly understood. Here, using spectroscopic and biochemical methods as well as cell-based assays, we report that chicken NANOG (cNANOG) oligomerizes through its CTD via a novel folding-upon-binding mechanism...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295862/perturbed-bone-composition-and-integrity-with-disorganized-osteoblast-function-in-zinc-receptor-gpr39-deficient-mice
#11
Milena Jovanovic, Felix N Schmidt, Gali Guterman-Ram, Hanifeh Khayyeri, Sahar Hiram-Bab, Ayelet Orenbuch, Svetlana Katchkovsky, Anastasia Aflalo, Hanna Isaksson, Björn Busse, Katharina Jähn, Noam Levaot
Changes in bone matrix composition are frequently found with bone diseases and may be associated with increased fracture risk. Bone is rich in the trace element zinc. Zinc was established to play a significant role in the growth, development, and maintenance of healthy bones; however, the mechanisms underlying zinc effects on the integrity of the skeleton are poorly understood. Here, we show that the zinc receptor (ZnR)/Gpr39 is required for normal bone matrix deposition by osteoblasts. Initial analysis showed that Gpr39-deficient (Gpr39-/- ) mice had weaker bones as a result of altered bone composition...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295861/splunc1-is-an-allosteric-modulator-of-the-epithelial-sodium-channel
#12
Christine Seulki Kim, Saira Ahmad, Tongde Wu, William G Walton, Matthew R Redinbo, Robert Tarran
Cystic fibrosis (CF) is a common genetic disease with significantly increased mortality. CF airways exhibit ion transport abnormalities, including hyperactivity of the epithelial Na+ channel (ENaC). Short-palate lung and nasal epithelial clone 1 (SPLUNC1) is a multifunctional innate defense protein that is secreted into the airway lumen. We have previously demonstrated that SPLUNC1 binds to and inhibits ENaC to maintain fluid homeostasis in airway epithelia and that this process fails in CF airways. Despite this, how SPLUNC1 actually regulates ENaC is unknown...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295860/reduced-ppar%C3%AE-2-expression-in-adipose-tissue-of-male-rat-offspring-from-obese-dams-is-associated-with-epigenetic-modifications
#13
Simon Lecoutre, Charlène Pourpe, Laura Butruille, Lucie Marousez, Christine Laborie, Céline Guinez, Jean Lesage, Didier Vieau, Jérôme Eeckhoute, Anne Gabory, Frédérik Oger, Delphine Eberlé, Christophe Breton
According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates program obesity later in life. White adipose tissue (WAT) has been the focus of developmental programming events, although underlying mechanisms remain elusive. In rodents, WAT development primarily occurs during lactation. We previously reported that adult rat offspring from dams fed a high-fat (HF) diet exhibited fat accumulation and decreased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels in WAT...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295859/structure-of-yidc-from-thermotoga-maritima-and-its-implications-for-yidc-mediated-membrane-protein-insertion
#14
Yanlong Xin, Yan Zhao, Jiangge Zheng, Haizhen Zhou, Xuejun Cai Zhang, Changlin Tian, Yihua Huang
The evolutionarily conserved YidC/Oxa1/Alb3 family of proteins represents a unique membrane protein family that facilitates the insertion, folding, and assembly of a cohort of α-helical membrane proteins in all kingdoms of life, yet its underlying mechanisms remain elusive. We report the crystal structures of the periplasmic domain (TmPD) and the full-length YidC (TmYidC) from Thermotoga maritima at a resolution of 2.5 and 3.8 Å, respectively. The crystal structure of TmPD reveals a β-supersandwich fold but with apparently shortened β strands and different connectivity, as compared to the periplasmic domain (EcPD) of Escherichia coli YidC (EcYidC)...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295858/hif-1%C3%AE-stabilization-reduces-retinal-degeneration-in-a-mouse-model-of-retinitis-pigmentosa
#15
Lorena Olivares-González, Cristina Martínez-Fernández de la Cámara, David Hervás, José María Millán, Regina Rodrigo
Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 (retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295857/defects-in-synaptic-transmission-at-the-neuromuscular-junction-precedes-motor-deficits-in-a-tdp-43q331k-transgenic-mouse-model-of-amyotrophic-lateral-sclerosis
#16
Kirat K Chand, Kah Meng Lee, John D Lee, Hao Qiu, Emily F Willis, Nickolas A Lavidis, Massimo A Hilliard, Peter G Noakes
Transactive response DNA-binding protein-43 (TDP-43) is involved in gene regulation via the control of RNA transcription, splicing, and transport. TDP-43 is a major protein component of ubiquinated inclusions that are found in amyotrophic lateral sclerosis (ALS); however, the function of TDP-43 at the neuromuscular junction (NMJ) and its role in ALS pathogenesis is largely unknown. Here, we show that TDP-43Q331K mutation in mice resulted in impaired neurotransmission by age 3 mo, preceding deficits in motor function and motor neuron loss, which were observed from age 10 mo...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295856/fgf21-induced-by-carbon-monoxide-mediates-metabolic-homeostasis-via-the-perk-atf4-pathway
#17
Yeonsoo Joe, Sena Kim, Hyo Jeong Kim, Jeongmin Park, Yingqing Chen, Hyeok-Jun Park, Seung-Joo Jekal, Stefan W Ryter, Uh Hyun Kim, Hun Taeg Chung
The prevalence of metabolic diseases, including type 2 diabetes, obesity, and cardiovascular disease, has rapidly increased, yet the molecular mechanisms underlying the metabolic syndrome, a primary risk factor, remain incompletely understood. The small, gaseous molecule carbon monoxide (CO) has well-known anti-inflammatory, antiproliferative, and antiapoptotic effects in a variety of cellular- and tissue-injury models, whereas its potential effects on the complex pathways of metabolic disease remain unknown...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295855/the-%C3%AE-2-agonist-terbutaline-specifically-decreases-pulmonary-arterial-pressure-under-normoxia-and-hypoxia-via-%C3%AE-adrenoceptor-antagonism
#18
Vanessa Neumann, Ralf Knies, Alexander Seidinger, Annika Simon, Kristina Lorenz, Michaela Matthey, Johannes Breuer, Daniela Wenzel
Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29282249/phosphate-dependent-luminal-atp-metabolism-regulates-transcellular-calcium-transport-in-intestinal-epithelial-cells
#19
Atsushi Uekawa, Hitoki Yamanaka, Liesbet Lieben, Yoshifumi Kimira, Mariko Uehara, Yoko Yamamoto, Shigeaki Kato, Kosei Ito, Geert Carmeliet, Ritsuko Masuyama
Extracellular low phosphate strongly enhances intestinal calcium absorption independently of active vitamin D [1,25(OH)2D3] signaling, but the underlying mechanisms remain poorly characterized. To elucidate the phosphate-dependent regulation of calcium transport, we investigated part of the enteral environment that is involved in 1,25(OH)2D3-independent calcium absorption, which responds to dietary phosphate levels in mice that lack intestinal vitamin D receptor (Vdr) activity. Impaired calcium absorption in intestinal Vdr-null mice was improved by dietary phosphate restriction...
December 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29279353/angiogenic-factor-imbalance-precedes-complement-deposition-in-placentae-of-the-bph-5-model-of-preeclampsia
#20
Jennifer L Sones, Audrey A Merriam, Angelina Seffens, Dex-Ann Brown-Grant, Scott D Butler, Anna M Zhao, Xinjing Xu, Carrie J Shawber, Jennifer K Grenier, Nataki C Douglas
Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality. Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH/5 implantation sites have transcriptomic alterations. Next-generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7...
December 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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