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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/30024792/mir-132-3p-boosts-caveolae-mediated-transcellular-transport-in-glioma-endothelial-cells-by-targeting-pten-pi3k-pkb-src-cav-1-signaling-pathway
#1
Yanting Gu, Ruiping Cai, Cai Zhang, Yixue Xue, Yali Pan, Jiahong Wang, Zhou Zhang
Blood-brain tumor barrier (BTB) impedes the transportation of antitumor therapeutic drugs into brain tumors. Its mechanism is still unknown, but learning how to improve the BTB permeability is critical for drug intervention. Recently, microRNAs (miRNAs) have appeared as regulation factors of numerous biologic processes and therapeutic targets of diverse diseases. In this study, we have identified that miR-132-3p is an essential miRNA by increasing the transcellular transport through the BTB. We found that miR-132-3p expression was significantly up-regulated in glioma endothelial cells (GECs)...
July 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30024791/interplay-between-sumoylation-and-neddylation-regulates-rpl11-localization-and-function
#2
Ahmed El Motiam, Santiago Vidal, Carlos F de la Cruz-Herrera, Sabela Da Silva-Álvarez, Maite Baz-Martínez, Rocío Seoane, Anxo Vidal, Manuel S Rodríguez, Dimitris P Xirodimas, Ana Sofia Carvalho, Hans Christian Beck, Rune Matthiesen, Manuel Collado, Carmen Rivas
The ribosomal protein L11 (RPL11) integrates different types of stress into a p53-mediated response. Here, we analyzed the impact of the ubiquitin-like protein SUMO on the RPL11-mouse double-minute 2 homolog-p53 signaling. We show that small ubiquitin-related modifier (SUMO)1 and SUMO2 covalently modify RPL11. We find that SUMO negatively modulates the conjugation of the ubiquitin-like protein neural precursor cell-expressed developmentally downregulated 8 (NEDD8) to RPL11 and promotes the translocation of the RP outside of the nucleoli...
July 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30024790/transient-activation-of-ampk-preceding-left-ventricular-pressure-overload-reduces-adverse-remodeling-and-preserves-left-ventricular-function
#3
Deok Hwa Nam, Eunah Kim, Ashley Benham, Hye-Kyung Park, Benjamin Soibam, George E Taffet, Jason T Kaelber, Ji Ho Suh, Heinrich Taegtmeyer, Mark L Entman, Erin L Reineke
Coordinated changes in signaling pathways and gene expression in hearts subjected to prolonged stress maintain cardiac function. Loss of steroid receptor coactivator-2 (SRC-2) results in a reversal to the fetal gene program and disrupts the response to pressure overload, accompanied by prominent effects on metabolism and growth signaling, including increased AMPK activation. We proposed that early metabolic stress driven by AMPK activation induces contractile dysfunction in mice lacking SRC-2. We used 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to activate AMPK transiently before transverse aortic constriction (TAC) in wild-type and cardiomyocyte-specific SRC-2 knockout (CKO) animals...
July 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30024789/nogo-a-promotes-inflammatory-heat-hyperalgesia-by-maintaining-trpv-1-function-in-the-rat-dorsal-root-ganglion-neuron
#4
Fang Hu, Huai-Cun Liu, Dong-Qiang Su, Hai-Jing Chen, Sun-On Chan, Yun Wang, Jun Wang
Nogo-A is a key inhibitory molecule of axon regeneration in oligodendrocytes. However, little is known about its role in adult neurons. In this study, we showed an important function of Nogo-A on regulation of inflammatory pain in dorsal root ganglion (DRG) neurons. In adult rats with complete Freund's adjuvant (CFA) hind paw inflammation, DRG neurons showed a significant increase in Nogo-A expression. Disruption of Nogo-A signaling with Nogo-66 receptor antagonist peptide, Nogo-A blocking antibody, Nogo-A short hairpin RNA, or Nogo-A gene knockout attenuated CFA-induced inflammatory heat hyperalgesia...
July 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30024788/a-novel-nutritional-intervention-improves-lung-function-in-overweight-obese-adolescents-with-poorly-controlled-asthma-the-supplemental-nutrition-in-asthma-control-snac-pilot-study
#5
Mustafa Bseikri, Joyce C McCann, Ashutosh Lal, Edward Fong, Kirsten Graves, Alisa Goldrich, Devan Block, Ginny L Gildengoren, Michele Mietus-Snyder, Mark Shigenaga, Jung Suh, Karen Hardy, Bruce N Ames
Asthma in the obese is often severe, difficult to treat, and characterized by less eosinophilic inflammation than asthma in the nonobese. Obesity-associated metabolic dysregulation may be a causal factor. We previously reported that a nutrient- and fiber-dense bar [Children's Hospital Oakland Research Institute (CHORI)-bar], which was designed to fill gaps in poor diets, improved metabolism in healthy overweight/obese (OW/OB) adults. In this pilot trial, OW/OB adolescents with poorly controlled asthma were randomized to weekly nutrition/exercise classes with or without twice-daily CHORI-bar consumption...
July 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30020833/integrated-communications-between-cyclooxygenase-2-and-alzheimer-s-disease
#6
Pei-Pei Guan, Pu Wang
Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandins (PGs) are involved in the pathogenesis of Alzheimer's disease (AD), which is characterized by the accumulation of β-amyloid protein (Aβ) and tau hyperphosphorylation. However, the gaps in our knowledge of the roles of COX-2 and PGs in AD have not been filled. Here, we summarized the literature showing that COX-2 dysregulation obviously influences abnormal cleavage of β-amyloid precursor protein, aggregation and deposition of Aβ in β-amyloid plaques and the inclusion of phosphorylated tau in neurofibrillary tangles...
July 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30020832/proinsulin-c-peptide-prevents-hyperglycemia-induced-vascular-leakage-and-metastasis-of-melanoma-cells-in-the-lungs-of-diabetic-mice
#7
Hye-Yoon Jeon, Yeon-Ju Lee, You-Sun Kim, Soo-Youl Kim, Eun-Taek Han, Won Sun Park, Seok-Ho Hong, Young-Myeong Kim, Kwon-Soo Ha
C-peptide has a beneficial effect against diabetic complications, but its role in hyperglycemia-induced metastasis is unknown. We investigated hyperglycemia-mediated pulmonary vascular leakage and metastasis and C-peptide inhibition of these molecular events using human pulmonary microvascular endothelial cells (HPMVECs) and streptozotocin-induced diabetic mice. VEGF, which is elevated in the lungs of diabetic mice, activated transglutaminase 2 (TGase2) in HPMVECs by sequential elevation of intracellular Ca2+ and reactive oxygen species (ROS) levels...
July 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30020831/understanding-the-coupling-between-dna-damage-detection-and-uvra-s-atpase-using-bulk-and-single-molecule-kinetics
#8
Jamie T Barnett, Neil M Kad
Nucleotide excision repair (NER) protects cells against diverse types of DNA damage, principally UV irradiation. In Escherichia coli, damage is recognized by 2 key enzymes: UvrA and UvrB. Despite extensive investigation, the role of UvrA's 2 ATPase domains in NER remains elusive. Combining single-molecule fluorescence microscopy and classic biochemical methods, we have investigated the role of nucleotide binding in UvrA's kinetic cycle. Measurement of UvrA's steady-state ATPase activity shows it is stimulated upon binding DNA ( kcat 0...
July 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30020830/differential-functional-selectivity-and-downstream-signaling-bias-of-ghrelin-receptor-antagonists-and-inverse-agonists
#9
Valerie T Ramirez, Wesley E P A van Oeffelen, Cristina Torres-Fuentes, Barbara Chruścicka, Clementine Druelle, Anna V Golubeva, Marcel van de Wouw, Timothy G Dinan, John F Cryan, Harriët Schellekens
The ghrelin receptor [growth hormone secretagogue receptor (GHSR)-1a] represents a promising pharmacologic target for the treatment of metabolic disorders, including obesity and cachexia, via central appetite modulation. The GHSR-1a has a complex pharmacology, highlighted by G-protein-dependent and -independent downstream signaling pathways and high basal constitutive activity. The functional selectivity and signaling bias of many GHSR-1a-specific ligands has not been fully characterized. In this study, we investigated the pharmacologic properties of ghrelin, MK-0677, L692,585, and [d-Lys3]-growth hormone-releasing peptide-6 (Dlys), JMV2959, and [d-Arg(1),d-Phe(5),d-Trp(7, 9),Leu(11)]-substance P (SP-analog)...
July 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30020829/secretory-phospholipase-a-2-group-iia-enhances-the-metabolic-rate-and-increases-glucose-utilization-in-response-to-thyroid-hormone
#10
Michael S Kuefner, Xiong Deng, Erin J Stephenson, Kevin Pham, Edwards A Park
Secretory phospholipase A2 group IIA (PLA2G2A) is a phospholipase which has a role in inflammation, atherogenesis, and host defense. Previously, we found that PLA2G2A protects mice on high-fat diets from weight gain and insulin resistance. Here, we examined the regulation of PLA2G2A and the metabolic changes that occur in response to variations in thyroid status. In particular, the impact of PLA2G2A on the brown adipose tissue (BAT) thermogenic gene expression was explored. We induced hypothyroidism in C57BL/6 and PLA2G2A-overexpressing (IIA+) mice over a 10 wk period or treated them with thyroid hormone (T3 ) for 5 wk...
July 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30020828/fat-storage-inducing-transmembrane-protein-2-fit2-is-less-abundant-in-type-2-diabetes-and-regulates-triglyceride-accumulation-and-insulin-sensitivity-in-adipocytes
#11
Madhur Agrawal, Chia Rou Yeo, Asim Shabbir, Vanna Chhay, David L Silver, Faidon Magkos, Antonio Vidal-Puig, Sue-Anne Toh
Fat storage-inducing transmembrane protein 2 (FIT2) aids in partitioning of cellular triacylglycerol into lipid droplets. A genome-wide association study reported FITM2-R3H domain containing like-HNF4A locus to be associated with type 2 diabetes (T2DM) in East Asian populations. Mice with adipose tissue (AT)-specific FIT2 knockout exhibited lipodystrophic features, with reduced AT mass, insulin resistance, and greater inflammation in AT when fed a high-fat diet. The role of FIT2 in regulating human adipocyte function is not known...
July 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30016600/sox4-is-involved-in-osteoarthritic-cartilage-deterioration-through-induction-of-adamts4-and-adamts5
#12
Yoshifumi Takahata, Eriko Nakamura, Kenji Hata, Makoto Wakabayashi, Tomohiko Murakami, Kanta Wakamori, Hiroshi Yoshikawa, Akio Matsuda, Naoshi Fukui, Riko Nishimura
Osteoarthritis is a common disease in joint cartilages. Because the molecular pathogenesis of osteoarthritis remains elusive, early diagnostic markers and effective therapeutic agents have not been developed. To understand the molecular mechanisms, we attempted to identify transcription factors involved in the onset of osteoarthritis. Microarray analysis of mouse articular cartilage cells indicated that retinoic acid, a destructive stimulus in articular cartilage, up-regulated expression of sex-determining region Y-box (Sox)4, a SoxC family transcription factor, together with increases in Adamts4 and Adamts5, both of which are aggrecanases of articular cartilages...
July 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30011231/chemosensory-bitter-taste-receptors-t2rs-are-activated-by-multiple-antibiotics
#13
Appalaraju Jaggupilli, Nisha Singh, Vivianne Cruz De Jesus, Mohamed Soussi Gounni, Premnath Dhanaraj, Prashen Chelikani
Many medications including antibiotics taste bitter. The potency of these antibiotics on the 25 bitter taste receptors (T2Rs) in humans remains poorly understood. Here we characterize by sensory and structure-function analyses how antibiotics frequently used to treat airway infections in cystic fibrosis activate multiple human T2Rs. The potency of the broad-spectrum antibiotics, tobramycin, levofloxacin, and azithromycin on the highly expressed T2Rs in airways, T2R4, T2R14, and T2R20 was pursued. The amino acids and structural features of T2R4, T2R14, and T2R20 important for antibiotic binding were characterized by mutational analysis in heterologous cell-based assays...
July 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30011230/segregation-of-dopamine-and-glutamate-release-sites-in-dopamine-neuron-axons-regulation-by-striatal-target-cells
#14
Guillaume M Fortin, Charles Ducrot, Nicolas Giguère, Willemieke M Kouwenhoven, Marie-Josée Bourque, Consiglia Pacelli, Rafael Koerich Varaschin, Marion Brill, Sherdeep Singh, Paul W Wiseman, Louis-Éric Trudeau
Dopamine (DA) is a key regulator of circuits controlling movement and motivation. A subset of midbrain DA neurons has been shown to express the vesicular glutamate transporter (VGLUT)2, underlying their capacity for glutamate release. Glutamate release is found mainly by DA neurons of the ventral tegmental area (VTA) and can be detected at terminals contacting ventral, but not dorsal, striatal neurons, suggesting the possibility that target-derived signals regulate the neurotransmitter phenotype of DA neurons...
July 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30004796/ectopic-expression-of-recipient-cd47-inhibits-mouse-macrophage-mediated-immune-rejection-against-human-stem-cell-transplants
#15
Cherry S Leung, Jiatao Li, Feng Xu, Alan S L Wong, Kathy O Lui
Like conventional transplants, immunosuppression is required to facilitate survival and function of human embryonic stem cell (hESC) derivatives after implantation into xenogeneic recipients. We have previously reported that T cells alone are sufficient to reject allogeneic murine ESC derivatives; and strategies that inhibit T-cell activation, including coreceptor and costimulation blockade, prevent hESC derivatives from being rejected. This study aimed to investigate, in addition to T cells, whether macrophages contribute to transplant rejection of hESC xenografts with nonobese diabetic (NOD)/SCID mice that lack functional T and B cells but have macrophages...
July 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30004795/microrna-31-5p-enhances-the-warburg-effect-via-targeting-fih
#16
Biying Zhu, Xiuye Cao, Wenqiang Zhang, Guoping Pan, Qing Yi, Wenbin Zhong, Daoguang Yan
The enhanced expression of miR-31 has been observed in many human malignancies including lung cancer, and this microRNA regulates several aspects of oncogenesis. However, the role of miR-31-5p in energy metabolism remains elusive. Here, we confirm that H1299 and A549 cells, 2 lung cancer cell lines, relay on aerobic glycolysis as main source of ATP. Inhibition of miR-31-5p leads to decreased glycolysis and ATP production, while miR-31-5p overexpression increases them. Hypoxia inducible factor 1 (HIF-1) up-regulates the expression of glycolytic enzymes, and the HIF-1α inhibitor (FIH) inhibits HIF-1 activity...
July 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30001168/lack-of-p11-expression-facilitates-acidity-sensing-function-of-task1-channels-in-mouse-adrenal-medullary-cells
#17
Masumi Inoue, Hidetada Matsuoka, Florian Lesage, Keita Harada
External acidity induces catecholamine secretion by inhibiting TASK1-like channels in rat adrenal medullary (AM) cells. TASK channels can function as a heteromer or homomer in the TASK subfamily. In this study, we elucidate the molecular identity of TASK1-like channels in mouse AM cells using gene knockout. Genetic deletion of TASK1, but not TASK3, abolished the depolarizing inward current and catecholamine secretion in response to acidity, whereas it did not affect the resting current level. Immunocytochemistry revealed that AM cells exhibited predominantly TASK1-like and little TASK3-like immunoreactivity...
July 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30001167/brahma-related-gene-1-brg1-contributes-to-liver-regeneration-by-epigenetically-activating-the-wnt-%C3%AE-catenin-pathway-in-mice
#18
Nan Li, Ming Kong, Sheng Zeng, Chenzhi Hao, Min Li, Luyang Li, Zheng Xu, Min Zhu, Yong Xu
Liver regeneration is a complicated pathophysiologic process that is regulated by a myriad of signaling pathways and transcription factors. The interaction among these pathways and factors, either cooperatively or antagonistically, may ultimately lead to recovery and restoration of liver function or permanent loss of liver function and liver failure. In the present study, we investigated the mechanism whereby the chromatin remodeling protein brahma related gene 1 (Brg1) regulates liver regeneration in mice...
July 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30001166/isocitrate-dehydrogenase-1-mutated-human-gliomas-depend-on-lactate-and-glutamate-to-alleviate-metabolic-stress
#19
Krissie Lenting, Mohammed Khurshed, Tom H Peeters, Corina N A M van den Heuvel, Sanne A M van Lith, Tessa de Bitter, Wiljan Hendriks, Paul N Span, Remco J Molenaar, Dennis Botman, Kiek Verrijp, Arend Heerschap, Mark Ter Laan, Benno Kusters, Anne van Ewijk, Martijn A Huynen, Cornelis J F van Noorden, William P J Leenders
Diffuse gliomas often carry point mutations in isocitrate dehydrogenase ( IDH1mut ), resulting in metabolic stress. Although IDHmut gliomas are difficult to culture in vitro, they thrive in the brain via diffuse infiltration, suggesting brain-specific tumor-stroma interactions that can compensate for IDH-1 deficits. To elucidate the metabolic adjustments in clinical IDHmut gliomas that contribute to their malignancy, we applied a recently developed method of targeted quantitative RNA next-generation sequencing to 66 clinical gliomas and relevant orthotopic glioma xenografts, with and without the endogenous IDH-1R132H mutation...
July 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29995440/unraveling-the-role-of-aurora-a-beyond-centrosomes-and-spindle-assembly-implications-in-muscle-differentiation
#20
Karthigeyan Dhanasekaran, Arnab Bose, Vinay J Rao, Ramachandran Boopathi, Shilpa Rani Shankar, Vinay Kumar Rao, Amrutha Swaminathan, Madavan Vasudevan, Reshma Taneja, Tapas K Kundu
Aurora kinases are critical mitotic serine/threonine kinases and are often implicated in tumorigenesis. Recent studies of the interphase functions for aurora kinase (Aurk)A have considerably expanded our understanding of its role beyond mitosis. To identify the unknown targets of AurkA, we used peptide array-based screening and found E2F4 to be a novel substrate. Phosphorylation of E2F4 by AurkA at Ser75 regulates its DNA binding and subcellular localization. Because E2F4 plays an important role in skeletal muscle differentiation, we attempted to gain insight into E2F4 phosphorylation in this context...
July 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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