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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/28223337/functional-expression-of-dopamine-d2-receptor-is-regulated-by-tetraspanin-7-mediated-postendocytic-trafficking
#1
Seol-Ae Lee, Yeongjun Suh, Saebom Lee, Jaehoon Jeong, Soo Jeong Kim, So Jung Kim, Sang Ki Park
The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28223336/variable-daxx-gene-methylation-is-a-common-feature-of-placental-trophoblast-differentiation-preeclampsia-and-response-to-hypoxia
#2
Boris Novakovic, Danièle Evain-Brion, Padma Murthi, Thiery Fournier, Richard Saffery
Placental functioning relies on the appropriate differentiation of progenitor villous cytotrophoblasts (CTBs) into extravillous cytotrophoblasts (EVCTs), including invasive EVCTs, and the multinucleated syncytiotrophoblast (ST) layer. This is accompanied by a general move away from a proliferative, immature phenotype. Genome-scale expression studies have provided valuable insight into genes that are associated with the shift to both an invasive EVCT and ST phenotype, whereas genome-scale DNA methylation analysis has shown that differentiation to ST involves widespread methylation shifts, which are counteracted by low oxygen...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28223335/cooperation-of-musashi-2-numb-mdm2-and-p53-in-drug-resistance-and-malignant-biology-of-pancreatic-cancer
#3
Weiwei Sheng, Ming Dong, Chuanping Chen, Zixin Wang, Yunwei Li, Kewei Wang, Yuji Li, Jianping Zhou
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2-mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and invivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28223334/corneal-surface-glycosylation-is-modulated-by-il-1r-and-pseudomonas-aeruginosa-challenge-but-is-insufficient-for-inhibiting-bacterial-binding
#4
Amber L Jolly, Paresh Agarwal, Matteo M E Metruccio, David R Spiciarich, David J Evans, Carolyn R Bertozzi, Suzanne M J Fleiszig
Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to P. aeruginosa adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated N-azidoacetylgalactosamine (Ac4GalNAz)...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28213359/methylation-of-the-phosphatase-transcription-activator-eya1-by-protein-arginine-methyltransferase-1-mechanistic-functional-and-structural-studies
#5
Xingguo Li, Allison Eberhardt, Jeanne N Hansen, Dirk Bohmann, Haitao Li, Nina F Schor
The eyes absent (EYA) family proteins are conserved transcriptional coactivators with intrinsic protein phosphatase activity. They play an essential role in the development of various organs in metazoans. These functions are associated with a unique combination of phosphatase and transactivation activities. However, it remains poorly understood how these activities and the consequent biologic functions of EYA are regulated. Here, we demonstrate that 2 conserved arginine residues, R304 and R306, of EYA1 are essential for its in vitro phosphatase activity and in vivo function during Drosophila eye development...
February 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28209774/methyl-donor-supplementation-alters-cognitive-performance-and-motivation-in-female-offspring-from-high-fat-diet-fed-dams
#6
Sarah E McKee, Nicola M Grissom, Christopher T Herdt, Teresa M Reyes
During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28209773/mannan-binding-lectin-a-serum-collectin-suppresses-t-cell-proliferation-via-direct-interaction-with-cell-surface-calreticulin-and-inhibition-of-proximal-t-cell-receptor-signaling
#7
Na Zhao, Jie Wu, Simin Xiong, Liyun Zhang, Xiao Lu, Shangliang Chen, Qifeng Wu, Hailan Wang, Ying Liu, Zhengliang Chen, Daming Zuo
Mannan binding lectin (MBL), initially described to activate the complement pathway, is also known to be involved in the pathogenesis of autoimmune diseases. We report a thus far unknown function of MBL as a suppressor of T-cell activation. MBL markedly inhibited T-cell proliferation induced by anti-CD3 and anti-CD28 antibodies. Moreover, the presence of MBL during T-cell priming interfered with proximal T-cell receptor signaling by decreasing phosphorylation of Lck, ZAP-70, and LAT. MBL bound to T cells through interaction between the collagen-like region of MBL and calreticulin (CRT) expressed on the T-cell surface...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28209772/maternal-smoke-exposure-decreases-mesenchymal-proliferation-and-modulates-rho-gtpase-dependent-actin-cytoskeletal-signaling-in-fetal-lungs
#8
Uchenna Unachukwu, Jordis Trischler, Monica Goldklang, Rui Xiao, Jeanine D'Armiento
The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m(3)) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28196897/role-of-hsp60-hspd1-in-diabetes-induced-renal-tubular-dysfunction-regulation-of-intracellular-protein-aggregation-atp-production-and-oxidative-stress
#9
Siripat Aluksanasuwan, Kanyarat Sueksakit, Kedsarin Fong-Ngern, Visith Thongboonkerd
Because underlying mechanisms of diabetic nephropathy/tubulopathy remained poorly understood, we aimed to define a key protein involving in hyperglycemia-induced renal tubular dysfunction. All altered renal proteins identified from previous large-scale proteome studies were subjected to global protein network analysis, which revealed heat shock protein 60 (HSP60, also known as HSPD1) as the central node of protein-protein interactions. Functional validation was performed using small interfering RNA (siRNA) to knock down HSP60 (siHSP60)...
February 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28193719/brain-specific-ablation-of-efr3a-promotes-adult-hippocampal-neurogenesis-via-the-brain-derived-neurotrophic-factor-pathway
#10
Qi Qian, Qiuji Liu, Dongming Zhou, Hongyu Pan, Zhiwei Liu, Fangping He, Suying Ji, Dongpi Wang, Wangxiao Bao, Xinyi Liu, Zhaoling Liu, Heng Zhang, Xiaoqin Zhang, Ling Zhang, Mingkai Wang, Ying Xu, Fude Huang, Benyan Lao, Binggui Sun
Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3a(f/f) mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology...
February 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28188179/new-insights-into-the-role-of-jmjd3-and-utx-in-axial-skeletal-formation-in-mice
#11
Chie Naruse, Shinwa Shibata, Masaru Tamura, Takayuki Kawaguchi, Kanae Abe, Kazushi Sugihara, Tomoaki Kato, Takumi Nishiuchi, Shigeharu Wakana, Masahito Ikawa, Masahide Asano
Jmjd3 and Utx are demethylases specific for lysine 27 of histone H3. Previous reports indicate that Jmjd3 is essential for differentiation of various cell types, such as macrophages and epidermal cells in mice, whereas Utx is involved in cancer and developmental diseases in humans and mice as well as Hox regulation in zebrafish and nematodes. Here, we report that Jmjd3, but not Utx, is involved in axial skeletal formation in mice. A Jmjd3 mutant embryo (Jmjd3(Δ18/Δ18)), but not a catalytically inactive Utx truncation mutant (Utx(-/y)), showed anterior homeotic transformation...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28188178/activation-of-the-hypoxia-inducible-factor-1%C3%AE-promotes-myogenesis-through-the-noncanonical-wnt-pathway-leading-to-hypertrophic-myotubes
#12
Federica Cirillo, Giulia Resmini, Andrea Ghiroldi, Marco Piccoli, Sonia Bergante, Guido Tettamanti, Luigi Anastasia
Regeneration of skeletal muscle is a complex process that requires the activation of quiescent adult stem cells, called satellite cells, which are resident in hypoxic niches in the tissue. Hypoxia has been recognized as a key factor to maintain stem cells in an undifferentiated state. Herein we report that hypoxia plays a fundamental role also in activating myogenesis. In particular, we found that the activation of the hypoxia-inducible factor (HIF)-1α under hypoxia, in murine skeletal myoblasts, leads to activation of MyoD through the noncanonical Wnt/β-catenin pathway...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28188177/automethylation-of-protein-arginine-methyltransferase-7-and-its-impact-on-breast-cancer-progression
#13
Pengyu Geng, Yu Zhang, Xiaoqing Liu, Na Zhang, Yingqi Liu, Xin Liu, Cong Lin, Xu Yan, Zhongwei Li, Guannan Wang, Yuxin Li, Jiang Tan, Dong-Xu Liu, Baiqu Huang, Jun Lu
Protein arginine methyltransferases (PRMTs) catalyze protein arginine methylation and are linked to carcinogenesis and metastasis. Some members of PRMTs have been found to undergo automethylation; however, the biologic significance of this self-modification is not entirely clear. In this report, we demonstrate that R531 of PRMT7 is self-methylated, both in vitro and in vivo Automethylation of PRMT7 plays a key role in inducing the epithelial-mesenchymal transition (EMT) program and in promoting the migratory and invasive behavior of breast cancer cells...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28188176/lectin-pathway-effector-enzyme-mannan-binding-lectin-associated-serine-protease-2-can-activate-native-complement-c3-in-absence-of-c4-and-or-c2
#14
Sadam Yaseen, Gregory Demopulos, Thomas Dudler, Munehisa Yabuki, Christi L Wood, W Jason Cummings, Larry W Tjoelker, Teizo Fujita, Steven Sacks, Peter Garred, Peter Andrew, Robert B Sim, Peter J Lachmann, Russell Wallis, Nicholas Lynch, Wilhelm J Schwaeble
All 3 activation pathways of complement-the classic pathway (CP), the alternative pathway, and the lectin pathway (LP)- converge into a common central event: the cleavage and activation of the abundant third complement component, C3, via formation of C3-activating enzymes (C3 convertases). The fourth complement component, C4, and the second component, C2, are indispensable constituents of the C3 convertase complex, C4bC2a, which is formed by both the CP and the LP. Whereas in the absence of C4, CP can no longer activate C3, LP retains a residual but physiologically critical capacity to convert native C3 into its activation fragments, C3a and C3b...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28188175/gcn5-determines-the-fate-of-drosophila-germline-stem-cells-through-degradation-of-cyclin-a
#15
Tianqi Liu, Qi Wang, Wenqing Li, Feiyu Mao, Shanshan Yue, Sun Liu, Xiaona Liu, Shan Xiao, Laixin Xia
The fluctuating CDK-CYCLIN complex plays a general role in cell-cycle control. Many types of stem cells use unique features of the cell cycle to facilitate asymmetric division. However, the manner in which these features are established remains poorly understood. The cell cycle of Drosophila female germline stem cells (GSCs) is characterized by short G1 and very long G2 phases, making it an excellent model for the study of cell cycle control in stem cell fate determination. Using a Drosophila female GSCs model, we found Gcn5, the first discovered histone acetyltransferase, to maintain germline stem cells in Drosophila ovaries...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28188174/brain-atrophy-in-picornavirus-infected-fvb-mice-is-dependent-on-the-h-2d-b-class-i-molecule
#16
April M Huseby Kelcher, Pascal A Atanga, Jeffrey D Gamez, Luz M Cumba Garcia, Stephanie J Teclaw, Kevin D Pavelko, Slobodan I Macura, Aaron J Johnson
Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill-defined. In this study, we evaluated the contribution of major histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)-infected transgenic FVB mice that express the D(b) class I molecule. FVB/D(b) and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2-weighted MRI and subsequent 3-dimensional volumetric analysis...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28188173/maresin-1-improves-insulin-sensitivity-and-attenuates-adipose-tissue-inflammation-in-ob-ob-and-diet-induced-obese-mice
#17
Leyre Martínez-Fernández, Pedro González-Muniesa, Laura M Laiglesia, Neira Sáinz, Pedro L Prieto-Hontoria, Xavier Escoté, Leticia Odriozola, Fernando J Corrales, Jose M Arbones-Mainar, José A Martínez, María J Moreno-Aliaga
The beneficial actions of n-3 fatty acids on obesity-induced insulin resistance and inflammation have been related to the synthesis of specialized proresolving lipid mediators (SPMs) like resolvins. The aim of this study was to evaluate the ability of one of these SPMs, maresin 1 (MaR1), to reverse adipose tissue inflammation and/or insulin resistance in two models of obesity: diet-induced obese (DIO) mice and genetic (ob/ob) obese mice. In DIO mice, MaR1 (2 μg/kg; 10 d) reduced F4/80-positive cells and expression of the proinflammatory M1 macrophage phenotype marker Cd11c in white adipose tissue (WAT)...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28183805/klotho-expression-in-long-bones-regulates-fgf23-production-during-renal-failure
#18
Jovana Kaludjerovic, Hirotaka Komaba, Tadatoshi Sato, Reinhold G Erben, Roland Baron, Hannes Olauson, Tobias E Larsson, Beate Lanske
Circulating levels of bone-derived fibroblast growth factor 23 (FGF23) increase early during acute and chronic kidney disease and are associated with adverse outcomes. Membrane-bound Klotho acts as a permissive coreceptor for FGF23, and its expression was recently found in osteoblasts/osteocytes. We hypothesized that Klotho in bone cells is part of an autocrine feedback loop that regulates FGF23 expression during renal failure. Thus, we induced renal failure in mice with targeted deletion of Klotho in long bones...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28183804/reduced-mitochondrial-activity-in-colonocytes-facilitates-ampk%C3%AE-2-dependent-inflammation
#19
Sandra Heller, Harrison M Penrose, Chloe Cable, Debjani Biswas, Hani Nakhoul, Melody Baddoo, Erik Flemington, Susan E Crawford, Suzana D Savkovic
Intestinal inflammation is associated with low levels of mucosal ATP, highlighting the importance of mitochondrial function associated with ATP production in the pathophysiology of the disease. In the inflamed colon of humans and mice, we found decreased levels of mitochondrial complex cytochrome c oxidase I/IV and lower ATP levels. Thus, we generated colonic ρ(0) cells with reduced mitochondrial function linked to ATP production by selective depletion of mitochondrial DNA. In these cells, RNA sequencing revealed a substantial number of differentially expressed transcripts, among which 240 belonged to inflammatory pathways activated in human inflamed colon and TNF-α-treated cells (false discovery rate < 0...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28183803/hexokinase-ii-derived-cell-penetrating-peptide-targets-mitochondria-and-triggers-apoptosis-in-cancer-cells
#20
Abiy D Woldetsadik, Maria C Vogel, Wael M Rabeh, Mazin Magzoub
Overexpression of mitochondria-bound hexokinase II (HKII) in cancer cells plays an important role in their metabolic reprogramming and protects them against apoptosis, thereby facilitating their growth and proliferation. Here, we show that covalently coupling a peptide that corresponds to the mitochondrial membrane-binding N-terminal domain of HKII (pHK) to a short, penetration-accelerating sequence (PAS) enhances the cellular uptake, mitochondrial localization, and cytotoxicity of the peptide in HeLa cells...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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