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https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#1
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27910985/uvb-radiation-vitamin-d-and-multiple-sclerosis
#2
H F DeLuca, L Plum
Acheson et al. (1960) observed an inverse relationship between sunlight exposure and the incidence of Multiple Sclerosis (MS). This led to the suggestion that increased levels of vitamin D caused by sunlight in some way suppresses MS. Further, super physiological doses of the metabolically active metabolite of vitamin D, i.e. 1α,25 dihydroxy vitamin D suppresses the animal model of MS i.e. experimental autoimmune encephalomyelitis (EAE). However, this response was accompanied by hypercalcemia. Hypercalcemia itself can suppress EAE...
December 2, 2016: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/27908915/-the-hypothalamic-glucagon-like-peptide-1-glp-1-receptor-glp-1r-is-sufficient-but-not-necessary-for-the-regulation-of-energy-balance-and-glucose-homeostasis-in-mice
#3
Melissa A Burmeister, Jennifer E Ayala, Hannah Smouse, Adriana Landivar-Rocha, Jacob D Brown, Daniel J Drucker, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the hypothalamic glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKD(ΔNkx2...
December 1, 2016: Diabetes
https://www.readbyqxmd.com/read/27907123/mice-hemizygous-for-a-pathogenic-mitofusin-2-allele-exhibit-hind-limb-foot-gait-deficits-and-phenotypic-perturbations-in-nerve-and-muscle
#4
Peter Bannerman, Travis Burns, Jie Xu, Laird Miers, David Pleasure
Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele...
2016: PloS One
https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#5
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
March 21, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906065/dystrophin-deficient-dogs-with-reduced-myostatin-have-unequal-muscle-growth-and-greater-joint-contractures
#6
Joe N Kornegay, Daniel J Bogan, Janet R Bogan, Jennifer L Dow, Jiahui Wang, Zheng Fan, Naili Liu, Leigh C Warsing, Robert W Grange, Mihye Ahn, Cynthia J Balog-Alvarez, Steven W Cotten, Monte S Willis, Candice Brinkmeyer-Langford, Hongtu Zhu, Joe Palandra, Carl A Morris, Martin A Styner, Kathryn R Wagner
BACKGROUND: Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition...
April 4, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905842/airway-smooth-muscle-cells-from-ovalbumin-sensitized-mice-show-increased-proliferative-response-to-tgf%C3%AE-1-due-to-up-regulation-of-smad3-and-tgf%C3%AE-rii
#7
Jianting Shi, Ming Chen, Lihua Ouyang, Linjie Huang, Xiaoling Lin, Wei Zhang, Ruiyun Liang, Zhiqiang Lv, Shanying Liu, Shanping Jiang
Transforming growth factor (TGF)-β1 is an important cytokine in airway remodeling in asthma. However, results of studies focusing on the effect of TGFβ1 on proliferation of airway smooth muscle cells (ASMCs) are controversial. This study aimed to elucidate the role of TGFβ1 signaling in the proliferation of ASMCs by establishing an allergic model that mimics airway remodeling in chronic asthma and cell culture. Cell proliferation was detected by viable cell counting and Cell Counting Kit (CCK)-8 analysis...
December 1, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/27904774/the-g-protein-coupled-chemoattractant-receptor-fpr2-promotes-malignant-phenotype-of-human-colon-cancer-cells
#8
Yi Xiang, Xiaohong Yao, Keqiang Chen, Xiafei Wang, Jiamin Zhou, Wanghua Gong, Teizo Yoshimura, Jiaqiang Huang, Rongquan Wang, Yuzhang Wu, Guochao Shi, Xiuwu Bian, Jiming Wang
The G-protein coupled chemoattractant receptor formylpeptide receptor-2 (FPR2 in human, Fpr2 in mice) is expressed by mouse colon epithelial cells and plays a critical role in mediating mucosal homeostasis and inflammatory responses. However, the biological role of FPR2 in human colon is unclear. Our investigation revealed that a considerable number of human colon cancer cell lines expressed FPR2 and its ligands promoted cell migration and proliferation. Human colon cancer cell lines expressing high levels of FPR2 also formed more rapidly growing tumors in immunocompromised mice as compared with cell lines expressing lower levels of FPR2...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903723/cerebellar-shank2-regulates-excitatory-synapse-density-motor-coordination-and-specific-repetitive-and-anxiety-like-behaviors
#9
Seungmin Ha, Dongwon Lee, Yi Sul Cho, Changuk Chung, Ye-Eun Yoo, Jihye Kim, Jiseok Lee, Woohyun Kim, Hyosang Kim, Yong Chul Bae, Keiko Tanaka-Yamamoto, Eunjoon Kim
: Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2(-/-) mice, remains unexplored. Here we show that Shank2(-/-) mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903722/adenosine-kinase-deficiency-in-the-brain-results-in-maladaptive-synaptic-plasticity
#10
Ursula S Sandau, Mariana Colino-Oliveira, Abbie Jones, Bounmy Saleumvong, Shayla Q Coffman, Long Liu, Catarina Miranda-Lourenço, Cátia Palminha, Vânia L Batalha, Yiming Xu, Yuqing Huo, Maria J Diógenes, Ana M Sebastião, Detlev Boison
: Adenosine kinase (ADK) deficiency in human patients (OMIM:614300) disrupts the methionine cycle and triggers hypermethioninemia, hepatic encephalopathy, cognitive impairment, and seizures. To identify whether this neurological phenotype is intrinsically based on ADK deficiency in the brain or if it is secondary to liver dysfunction, we generated a mouse model with a brain-wide deletion of ADK by introducing a Nestin-Cre transgene into a line of conditional ADK deficient Adk(fl/fl) mice...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27900018/influence-of-ezrin-shrna-in-combination-with-hsp70-on-the-apoptosis-and-proliferation-of-osteosarcoma-cells
#11
Qin Yao, Yihua Pei, Huiqin Zhuo, Bozhen Xie
Ezrin and heat shock protein (HSP)70 have been reported to regulate cell apoptosis and tumor development of osteosarcoma. However, there has not been reported the synergy effect of knocking down ezrin and overexpressing HSP70. In the present study, two vectors, pGFP-V-RS-shRNA and pGFP-V-RS-shRNA-HSP70, were constructed and transfected into LM8 cells [denoted as small hairpin (sh)RNA group and dual group, respectively]. The apoptosis rates in these two transfected groups were significantly higher than those in the control group (empty vector) (P=0...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898698/myeloid-dll4-does-not-contribute-to-the-pathogenesis-of-non-alcoholic-steatohepatitis-in-ldlr-mice
#12
Mike L J Jeurissen, Sofie M A Walenbergh, Tom Houben, Tim Hendrikx, Jieyi Li, Yvonne Oligschlaeger, Patrick J van Gorp, Marion J J Gijbels, Albert Bitorina, Isabell Nessel, Freddy Radtke, Marc Vooijs, Jan Theys, Ronit Shiri-Sverdlov
Non-alcoholic steatohepatitis (NASH) is characterized by liver steatosis and inflammation. Currently, the underlying mechanisms leading to hepatic inflammation are not fully understood and consequently, therapeutic options are poor. Non-alcoholic steatohepatitis (NASH) and atherosclerosis share the same etiology whereby macrophages play a key role in disease progression. Macrophage function can be modulated via activation of receptor-ligand binding of Notch signaling. Relevantly, global inhibition of Notch ligand Delta-Like Ligand-4 (DLL4) attenuates atherosclerosis by altering the macrophage-mediated inflammatory response...
2016: PloS One
https://www.readbyqxmd.com/read/27898407/expression-pattern-and-regulatory-role-of-microrna-23a-in-conjugated-linoleic-acids-induced-apoptosis-of-adipocytes
#13
Renli Qi, Qi Wang, Jing Wang, Jinxiu Huang, Shan Jiang, Rong Xiao, Zuohua Liu, Feiyun Yang
BACKGROUND/AIMS: Conjugated linoleic acids (CLAs) are known to induce apoptosis in adipocytes; however, the cellular mechanisms involved remained illdefined. We explored the different apoptotic induction effects of two CLA isomers on adipocytes and then investigated the expression and function of microRNAs (miRNAs) related to the apoptosis. METHODS: TUNEL and FCM assays were used to detect CLAs-induced adipocyte apoptosis. Microarrays were used to compare the differential expression of miRNAs...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27897970/an-essential-cell-autonomous-role-for-hepcidin-in-cardiac-iron-homeostasis
#14
Samira Lakhal-Littleton, Magda Wolna, Yu Jin Chung, Helen C Christian, Lisa C Heather, Marcella Brescia, Vicky Ball, Rebeca Diaz, Ana Santos, Daniel Biggs, Kieran Clarke, Benjamin Davies, Peter A Robbins
Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27894913/the-regulation-of-cellular-apoptosis-by-the-ros-triggered-perk-eif2%C3%AE-chop-pathway-plays-a-vital-role-in-bisphenol-a-induced-male-reproductive-toxicity
#15
Li Yin, Yanlin Dai, Zhihong Cui, Xiao Jiang, Wenbin Liu, Fei Han, Ao Lin, Jia Cao, Jinyi Liu
Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effects of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate...
November 25, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27894619/expression-of-pro-fibrotic-and-anti-fibrotic-molecules-in-dimethylnitrosamine-induced-hepatic-fibrosis
#16
Roberta Sferra, Antonella Vetuschi, Simona Pompili, Eugenio Gaudio, Silvia Speca, Giovanni Latella
BACKGROUND: Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, produced by activated myofibroblasts which are modulated by both profibrotic and antifibrotic factors. OBJECTIVE: To evaluate in vivo the expression of pro-fibrotic molecules like avβ6 integrin, transforming growth factor-β (TGF-β), Smad3, connective tissue growth factor (CTGF) and mammalian target of Rapamycin (mTOR), as well as anti-fibrotic peroxisome proliferator-activated receptor-γ (PPARγ) in an experimental model of chronic hepatitis-associated fibrosis induced by intraperitoneal administration of dimethylnitrosamine (DMN) in mice...
November 11, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27893709/identification-of-myst3-as-a-novel-epigenetic-activator-of-er%C3%AE-frequently-amplified-in-breast-cancer
#17
L Yu, Y Liang, X Cao, X Wang, H Gao, S-Y Lin, R Schiff, X-S Wang, K Li
Estrogen receptor α (ERα) is a master driver of a vast majority of breast cancers. Breast cancer cells often develop resistance to endocrine therapy via restoration of the ERα activity through survival pathways. Thus identifying the epigenetic activator of ERα that can be targeted to block ERα gene expression is a critical topic of endocrine therapy. Here, integrative genomic analysis identified MYST3 as a potential oncogene target that is frequently amplified in breast cancer. MYST3 is involved in histone acetylation via its histone acetyltransferase domain (HAT) and, as a result, activates gene expression by altering chromatin structure...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27893707/blockade-of-the-il-6-trans-signalling-stat3-axis-suppresses-cachexia-in-kras-induced-lung-adenocarcinoma
#18
A Miller, L McLeod, S Alhayyani, A Szczepny, D N Watkins, W Chen, P Enriori, W Ferlin, S Ruwanpura, B J Jenkins
Lung cancer is the leading cause of cancer death worldwide, and is frequently associated with the devastating paraneoplastic syndrome of cachexia. The potent immunomodulatory cytokine interleukin (IL)-6 has been linked with the development of lung cancer as well as cachexia; however, the mechanisms by which IL-6 promotes muscle wasting in lung cancer cachexia are ill-defined. In this study, we report that the gp130(F/F) knock-in mouse model displaying hyperactivation of the latent transcription factor STAT3 via the common IL-6 cytokine family signalling receptor, gp130, develops cachexia during Kras-driven lung carcinogenesis...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889641/increased-mitochondrial-superoxide-in-the-brain-but-not-periphery-sensitizes-mice-to-angiotensin-ii-mediated-hypertension
#19
Adam J Case, Jun Tian, Matthew C Zimmerman
Angiotensin II (AngII) elicits the production of superoxide (O2(•-)) from mitochondria in numerous cell types within peripheral organs and in the brain suggesting a role for mitochondrial-produced O2(•-) in the pathogenesis of hypertension. However, it remains unclear if mitochondrial O2(•-) is causal in the development of AngII-induced hypertension, or if mitochondrial O2(•-) in the absence of elevated AngII is sufficient to increase blood pressure. Further, the tissue specific (i.e. central versus peripheral) redox regulation of AngII hypertension remains elusive...
November 20, 2016: Redox Biology
https://www.readbyqxmd.com/read/27889058/mutations-in-reep6-cause-autosomal-recessive-retinitis-pigmentosa
#20
Gavin Arno, Smriti A Agrawal, Aiden Eblimit, James Bellingham, Mingchu Xu, Feng Wang, Christina Chakarova, David A Parfitt, Amelia Lane, Thomas Burgoyne, Sarah Hull, Keren J Carss, Alessia Fiorentino, Matthew J Hayes, Peter M Munro, Ralph Nicols, Nikolas Pontikos, Graham E Holder, Chinwe Asomugha, F Lucy Raymond, Anthony T Moore, Vincent Plagnol, Michel Michaelides, Alison J Hardcastle, Yumei Li, Catherine Cukras, Andrew R Webster, Michael E Cheetham, Rui Chen
Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families...
November 17, 2016: American Journal of Human Genetics
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