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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/28096235/role-of-cardiotrophin-1-in-the-regulation-of-metabolic-circadian-rhythms-and-adipose-core-clock-genes-in-mice-and-characterization-of-24-h-circulating-ct-1-profiles-in-normal-weight-and-overweight-obese-subjects
#1
Miguel López-Yoldi, Kimber L Stanhope, Marta Garaulet, X Guoxia Chen, Beatriz Marcos-Gómez, María Paz Carrasco-Benso, Eva M Santa Maria, Xavier Escoté, Vivien Lee, Marinelle V Nunez, Valentina Medici, Eduardo Martínez-Ansó, Neira Sáinz, Ana E Huerta, Laura M Laiglesia, Jesús Prieto, J Alfredo Martínez, Matilde Bustos, Peter J Havel, Maria J Moreno-Aliaga
Cardiotrophin (CT)-1 is a regulator of glucose and lipid homeostasis. In the present study, we analyzed whether CT-1 also acts to peripherally regulate metabolic rhythms and adipose tissue core clock genes in mice. Moreover, the circadian pattern of plasma CT-1 levels was evaluated in normal-weight and overweight subjects. The circadian rhythmicity of oxygen consumption rate (Vo2) was disrupted in aged-obese CT-1-deficient (CT-1(-/-)) mice (12 mo). Although circadian rhythms of Vo2 were conserved in young-lean CT-1(-/-) mice (2 mo), CT-1 deficiency caused a phase shift of the acrophase...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28096234/glutamate-oxaloacetate-transaminase-enables-anaplerotic-refilling-of-tca-cycle-intermediates-in-stroke-affected-brain
#2
Cameron Rink, Surya Gnyawali, Richard Stewart, Seth Teplitsky, Hallie Harris, Sashwati Roy, Chandan K Sen, Savita Khanna
Ischemic stroke results in excessive release of glutamate, which contributes to neuronal cell death. Here, we test the hypothesis that otherwise neurotoxic glutamate can be productively metabolized by glutamate oxaloacetate transaminase (GOT) to maintain cellular energetics and protect the brain from ischemic stroke injury. The GOT-dependent metabolism of glutamate was studied in primary neural cells and in stroke-affected C57-BL6 mice using magnetic resonance spectroscopy and GC-MS. Extracellular Glu sustained cell viability under hypoglycemic conditions and increased GOT-mediated metabolism in vitro Correction of stroke-induced hypoxia using supplemental oxygen in vivo lowered Glu levels as measured by (1)H magnetic resonance spectroscopy...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28096233/role-of-the-constant-region-domain-in-the-structural-diversity-of-human-antibody-light-chains
#3
Emi Hifumi, Hiroaki Taguchi, Ryuichi Kato, Taizo Uda
Issues regarding the structural diversity (heterogeneity) of an antibody molecule have been the subject of discussion along with the development of antibody drugs. Research on heterogeneity has been extensive in recent years, but no clear solution has been reached. Heterogeneity is also observed in catalytic antibody κ light chains (CLs). In this study, we investigated how the constant region domain of CLs concerns structural diversity because it is a simple and good example for elucidating heterogeneity. By means of cation-exchange chromatography, SDS-PAGE, and 2-dimensional electrophoresis for the CL, multimolecular forms consisting of different electrical charges and molecular sizes coexisted in the solution, resulting in the similar heterogeneity of the full length of CLs...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28096232/pr-957-a-selective-inhibitor-of-immunoproteasome-subunit-low-mw-polypeptide-7-attenuates-experimental-autoimmune-neuritis-by-suppressing-th17-cell-differentiation-and-regulating-cytokine-production
#4
Haijie Liu, Chunxiao Wan, Yanan Ding, Ranran Han, Yating He, Jinting Xiao, Junwei Hao
Experimental autoimmune neuritis (EAN) is a CD4(+) T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28096231/roles-of-5-lipoxygenase-and-cyclooxygenase-2-in-the-biosynthesis-of-hemiketals-e2-and-d2-by-activated-human-leukocytes
#5
Juan A Giménez-Bastida, Takahiro Shibata, Koji Uchida, Claus Schneider
The 2 hemiketal (HK) eicosanoids HKD2 and HKE2 are the major products of the biosynthetic crossover of the 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) pathways. HKs result from the rearrangement of a di-endoperoxide intermediate formed in the COX-2-dependent oxygenation of 5S-hydroxyeicosatetraenoic acid (5S-HETE). We analyzed HK biosynthesis in human leukocytes stimulated ex vivo and defined the biosynthetic roles of 5-LOX and COX-2, using inhibitors and incubations with exogenous substrates. Activation of leukocytes with LPS followed by treatment with the calcium ionophore A23187 resulted in the formation of PGE2, 5-HETE, and LTB4 as the principal metabolites of COX-2 and 5-LOX, respectively...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28087575/treating-inflammation-and-infection-in-the-21st-century-new-hints-from-decoding-resolution-mediators-and-mechanisms
#6
REVIEW
Charles N Serhan
Practitioners of ancient societies from the time of Hippocrates and earlier recognized and treated the signs of inflammation, heat, redness, swelling, and pain with agents that block or inhibit proinflammatory chemical mediators. More selective drugs are available today, but this therapeutic concept has not changed. Because the acute inflammatory response is host protective to contain foreign invaders, much of today's pharmacopeia can cause serious unwanted side effects, such as immune suppression. Uncontrolled inflammation is now considered pathophysiologic and is associated with many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity, and asthma, as well as classic inflammatory diseases (e...
January 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28082354/combination-therapy-with-liposomal-neuroprotectants-and-tissue-plasminogen-activator-for-treatment-of-ischemic-stroke
#7
Tatsuya Fukuta, Tomohiro Asai, Yosuke Yanagida, Mio Namba, Hiroyuki Koide, Kosuke Shimizu, Naoto Oku
For ischemic stroke treatment, extension of the therapeutic time window (TTW) of thrombolytic therapy with tissue plasminogen activator (tPA) and amelioration of secondary ischemia/reperfusion (I/R) injury are most desirable. Our previous studies have indicated that liposomal delivery of neuroprotectants into an ischemic region is effective for stroke treatment. In the present study, for solving the above problems in the clinical setting, the usefulness of combination therapy with tPA and liposomal Fasudil (Fasudil-Lip) was investigated in ischemic stroke model rats with photochemically induced thrombosis, with clots that were dissolved by tPA...
January 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28082353/gestational-disruptions-in-metabolic-rhythmicity-of-the-liver-muscle-and-placenta-affect-fetal-size
#8
Georgia Papacleovoulou, Vanya Nikolova, Olayiwola Oduwole, Jenny Chambers, Marta Vazquez-Lopez, Eugene Jansen, Kypros Nicolaides, Malcolm Parker, Catherine Williamson
Maternal metabolic adaptations are essential for successful pregnancy outcomes. We investigated how metabolic gestational processes are coordinated, whether there is a functional link with internal clocks, and whether disruptions are related to metabolic abnormalities in pregnancy, by studying day/night metabolic pathways in murine models and samples from pregnant women with normally grown and large-for-gestational age infants. In early mouse pregnancy, expression of hepatic lipogenic genes was up-regulated and uncoupled from the hepatic clock...
January 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28082352/estrogen-receptor-%C3%AE-is-required-for-oviductal-transport-of-embryos
#9
Shuai Li, Sofia R S O'Neill, Yong Zhang, Michael J Holtzman, Ken-Ichi Takemaru, Kenneth S Korach, Wipawee Winuthayanon
Newly fertilized embryos spend the first few days within the oviduct and are transported to the uterus where they implant onto the uterine wall. An implantation of the embryo before reaching the uterus could result in ectopic pregnancy and lead to maternal death. Estrogen is necessary for embryo transport in mammals; however, the mechanism involved in estrogen-mediated cellular function within the oviduct remains unclear. In this study, we show in mouse models that ciliary length and beat frequency of the oviductal epithelial cells are regulated through estrogen receptor α (ESR1) but not β (ESR2)...
January 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28082351/fty720-fingolimod-increases-npc1-and-npc2-expression-and-reduces-cholesterol-and-sphingolipid-accumulation-in-niemann-pick-type-c-mutant-fibroblasts
#10
Jason Newton, Nitai C Hait, Michael Maceyka, Alexandria Colaco, Melissa Maczis, Christopher A Wassif, Antony Cougnoux, Forbes D Porter, Sheldon Milstien, Nicholas Platt, Frances M Platt, Sarah Spiegel
Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder caused by mutations in NPC1 or NPC2 with decreased functions leading to lysosomal accumulation of cholesterol and sphingolipids. FTY720/fingolimod, used for treatment of multiple sclerosis, is phosphorylated by nuclear sphingosine kinase 2 and its active phosphorylated form (FTY720-P) is an inhibitor of class I histone deacetylases. In this study, administration of clinically relevant doses of FTY720 to mice increased expression of NPC1 and -2 in brain and liver and decreased cholesterol in an SphK2-dependent manner...
January 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28082350/secretin-is-involved-in-sodium-conservation-through-the-renin-angiotensin-aldosterone-system
#11
Juan Bai, Billy K C Chow
Secretin (SCT) and its receptor (SCTR) are important in fluid regulation at multiple levels via the modulation of expression and translocation of renal aquaporin 2 and functions of central angiotensin II (ANGII). The functional interaction of SCT with peripheral ANGII, however, remains unknown. As the ANGII-aldosterone axis dominates the regulation of renal epithelial sodium channel (ENaC) function, we therefore tested whether SCT/SCTR can regulate sodium homeostasis via the renin-angiotensin-aldosterone system...
January 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28077425/metastasis-suppressor-nm23-limits-oxidative-stress-in-mammals-by-preventing-activation-of-stress-activated-protein-kinases-jnks-through-its-nucleoside-diphosphate-kinase-activity
#12
Evelyne Peuchant, Marie-Lise Bats, Isabelle Moranvillier, Michel Lepoivre, Jérôme Guitton, Dominique Wendum, Marie-Lise Lacombe, François Moreau-Gaudry, Mathieu Boissan, Sandrine Dabernat
NME1 (nonmetastatic expressed 1) gene, which encodes nucleoside diphosphate kinase (NDPK) A [also known as nonmetastatic clone 23 (NM23)-H1 in human and NM23-M1 in mouse], is a suppressor of metastasis, but several lines of evidence-mostly from plants-also implicate it in the regulation of the oxidative stress response. Here, our aim was to investigate the physiologic relevance of NDPK A with respect to the oxidative stress response in mammals and to study its molecular basis. NME1 knockout mice died sooner, suffered greater hepatocyte injury, and had lower superoxide dismutase activity than did wild-type (WT) mice in response to paraquat-induced acute oxidative stress...
January 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28073836/ionotropic-glutamate-receptors-activate-cell-signaling-in-response-to-glutamate-in-schwann-cells
#13
Wendy M Campana, Elisabetta Mantuano, Pardis Azmoon, Kenneth Henry, Michael A Banki, John H Kim, Donald P Pizzo, Steven L Gonias
In the peripheral nervous system, Schwann cells (SCs) demonstrate surveillance activity, detecting injury and undergoing trans-differentiation to support repair. SC receptors that detect peripheral nervous system injury remain incompletely understood. We used RT-PCR to profile ionotropic glutamate receptor expression in cultured SCs. We identified subunits required for assembly of N-methyl-d-aspartic acid (NMDA) receptors (NMDA-R), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and kainate receptors...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28073835/mechanosensitive-transient-receptor-potential-vanilloid-4-regulates-dermatophagoides-farinae-induced-airway-remodeling-via-2-distinct-pathways-modulating-matrix-synthesis-and-degradation
#14
Farai Gombedza, Vinay Kondeti, Nosayba Al-Azzam, Stephanie Koppes, Ernest Duah, Prachi Patil, Madison Hexter, Daniel Phillips, Charles K Thodeti, Sailaja Paruchuri
Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4 knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4 knockout mice showed diminished differentiation potential compared with wild-type mice...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28073834/dynamic-and-coordinated-single-molecular-interactions-at-tm4sf5-enriched-microdomains-guide-invasive-behaviors-in-2-and-3-dimensional-environments
#15
Hye-Jin Kim, Sojung Kwon, Seo Hee Nam, Jae Woo Jung, Minkyung Kang, Jihye Ryu, Ji Eon Kim, Jin-Gyu Cheong, Chang Yun Cho, Somi Kim, Dae-Geun Song, Yong-Nyun Kim, Tai Young Kim, Min-Kyo Jung, Kyung-Min Lee, Chan-Gi Pack, Jung Weon Lee
Membrane proteins sense extracellular cues and transduce intracellular signaling to coordinate directionality and speed during cellular migration. They are often localized to specific regions, as with lipid rafts or tetraspanin-enriched microdomains; however, the dynamic interactions of tetraspanins with diverse receptors within tetraspanin-enriched microdomains on cellular surfaces remain largely unexplored. Here, we investigated effects of tetraspan(in) TM4SF5 (transmembrane 4 L six family member 5)-enriched microdomains (T5ERMs) on the directionality of cell migration...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#16
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069827/melatonin-mediated-upregulation-of-glut1-blocks-exit-from-pluripotency-by-increasing-the-uptake-of-oxidized-vitamin-c-in-mouse-embryonic-stem-cells
#17
Haibo Wu, Chao Song, Jingcheng Zhang, Jiamin Zhao, Beibei Fu, Tingchao Mao, Yong Zhang
Melatonin and vitamin C are powerful antioxidants that improve the reprogramming efficiency of induced pluripotent stem cells (iPSCs). However, the effects of the combined treatment of vitamin C and melatonin on the differentiation of embryonic stem cells (ESCs) have not yet been examined. In this study, we showed that melatonin synergizes with vitamin C to derail exit from pluripotency of mouse ESCs. This effect is related to the increased uptake of dehydroascorbate, the oxidized form of vitamin C, through glucose transporter 1 (Glut1) transporter, which in turn, is upregulated by melatonin treatment...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#18
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069825/intravenous-anesthetic-propofol-binds-to-5-lipoxygenase-and-attenuates-leukotriene-b4-production
#19
Toshiaki Okuno, Sophia Koutsogiannaki, Mai Ohba, Matthew Chamberlain, Weiming Bu, Fu-Yan Lin, Roderic G Eckenhoff, Takehiko Yokomizo, Koichi Yuki
Propofol is an intravenous anesthetic that produces its anesthetic effect, largely via the GABAA receptor in the CNS, and also reduces the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil respiratory burst. Because fMLP-stimulated neutrophils produce leukotriene (LT)B4, we examined the effect of propofol on LTB4 production in vivo and in vitro Cecal ligation and puncture surgery was performed in mice, with or without exposure to propofol. Propofol attenuated the production of 5-lipoxygenase (5-LOX)-related arachidonic acid (AA) derivatives in the peritoneal fluid...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28062540/adiponectin-association-with-t-cadherin-protects-against-neointima-proliferation-and-atherosclerosis
#20
Yuya Fujishima, Norikazu Maeda, Keisuke Matsuda, Shigeki Masuda, Takuya Mori, Shiro Fukuda, Ryohei Sekimoto, Masaya Yamaoka, Yoshinari Obata, Shunbun Kita, Hitoshi Nishizawa, Tohru Funahashi, Barbara Ranscht, Iichiro Shimomura
Adiponectin, an adipocyte-derived protein abundant in the circulation, is thought to be protective against atherosclerosis. However, it is not fully understood how the association of adiponectin with vascular cells and its antiatherogenic effect are connected. In this study, T-cadherin was essential for accumulation of adiponectin in the neointima and atherosclerotic plaque lesions, and the adiponectin-T-cadherin association protected against vascular injury. In the apolipoprotein E-knockout (ApoE-KO) mice, adiponectin, and T-cadherin colocalized on endothelial cells and synthetic smooth muscle cells in the aortic intima...
January 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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