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https://www.readbyqxmd.com/read/28107769/the-transcriptional-modulator-ifrd1-controls-pgc-1%C3%AE-expression-under-short-term-adrenergic-stimulation-in-brown-adipocytes
#1
Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Nakamura, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue, and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue. Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous white adipose tissues, but not in epididymal visceral white adipose tissue, in vivo...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28103427/repeated-maximal-intensity-hypoxic-exercise-superimposed-to-hypoxic-residence-boosts-skeletal-muscle-transcriptional-responses-in-elite-team-sport-athletes
#2
Franck Brocherie, Grégoire P Millet, Gommaar D'Hulst, Ruud Van Thienen, Louise Deldicque, Olivier Girard
AIM: To determine whether repeated maximal-intensity hypoxic exercise induces larger beneficial adaptations on the hypoxia inducible factor-1α pathway and its target genes than similar normoxic exercise, when combined with chronic hypoxic exposure. METHODS: Lowland elite male team-sport athletes underwent 14 days of passive normobaric hypoxic exposure (≥14 h.day(-1) at Fi O2 14.5-14.2%) with the addition of six maximal-intensity exercise sessions either in normobaric hypoxia (Fi O2 ~14...
January 19, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28100774/loss-of-cyclin-dependent-kinase-2-in-the-pancreas-links-primary-%C3%AE-cell-dysfunction-to-progressive-depletion-of-%C3%AE-cell-mass-and-diabetes
#3
So Yoon Kim, Ji-Hyeon Lee, Matthew J Merrins, Oksana Gavrilova, Xavier Bisteau, Philipp Kaldis, Leslie S Satin, Sushil G Rane
The failure of pancreatic islet β-cells is a major contributor to the etiology of Type 2 diabetes. β-cell dysfunction and declining β-cell mass are two mechanisms that contribute to this failure, although it is unclear if they are molecularly linked. Here, we show that the cell cycle regulator, cyclin-dependent kinase 2 (Cdk2), couples primary β-cell dysfunction to the progressive deterioration of β-cell mass in diabetes. Mice with pancreas-specific deletion of Cdk2 are glucose intolerant primarily due to defects in glucose-stimulated insulin secretion...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28099124/browning-of-white-adipose-tissue-lessons-from-experimental-models
#4
Thereza Cristina Lonzetti Bargut, Vanessa Souza-Mello, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis. This phenomenon is known as browning and is more likely to occur in subcutaneous fat depots. Browning involves the expression of many transcription factors, such as PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor (PPAR)-γ, and of uncoupling protein (UCP)-1, which is the hallmark of thermogenesis...
January 18, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28096382/mitochondrial-activation-chemicals-synergize-with-surface-receptor-pd-1-blockade-for-t-cell-dependent-antitumor-activity
#5
Kenji Chamoto, Partha S Chowdhury, Alok Kumar, Kazuhiro Sonomura, Fumihiko Matsuda, Sidonia Fagarasan, Tasuku Honjo
Although immunotherapy by PD-1 blockade has dramatically improved the survival rate of cancer patients, further improvement in efficacy is required to reduce the fraction of less sensitive patients. In mouse models of PD-1 blockade therapy, we found that tumor-reactive cytotoxic T lymphocytes (CTLs) in draining lymph nodes (DLNs) carry increased mitochondrial mass and more reactive oxygen species (ROS). We show that ROS generation by ROS precursors or indirectly by mitochondrial uncouplers synergized the tumoricidal activity of PD-1 blockade by expansion of effector/memory CTLs in DLNs and within the tumor...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28091351/supplementing-the-maternal-diet-of-rats-with-butyrate-enhances-mitochondrial-biogenesis-in-the-skeletal-muscles-of-weaned-offspring
#6
Yanping Huang, Shixing Gao, Guo Jun, Ruqian Zhao, Xiaojing Yang
The present study aimed to investigate the effects of maternal dietary butyrate supplementation on energy metabolism and mitochondrial biogenesis in offspring skeletal muscle and the possible mediating mechanisms. Virgin female rats were randomly assigned to either control or butyrate diets (1 % butyrate sodium) throughout gestation and lactation. At the end of lactation (21 d), the offspring were killed by exsanguination from the abdominal aorta under anaesthesia. The results showed that maternal butyrate supplementation throughout gestation and lactation did not affect offspring body weight...
January 16, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28090760/expression-patterns-of-cardiac-aging-in-drosophila
#7
Leah Cannon, Alexander C Zambon, Anthony Cammarato, Zhi Zhang, Georg Vogler, Matthew Munoz, Erika Taylor, Jérôme Cartry, Sanford I Bernstein, Simon Melov, Rolf Bodmer
Aging causes cardiac dysfunction, often leading to heart failure and death. The molecular basis of age-associated changes in cardiac structure and function is largely unknown. The fruit fly, Drosophila melanogaster, is well-suited to investigate the genetics of cardiac aging. Flies age rapidly over the course of weeks, benefit from many tools to easily manipulate their genome, and their heart has significant genetic and phenotypic similarities to the human heart. Here, we performed a cardiac-specific gene expression study on aging Drosophila and carried out a comparative meta-analysis with published rodent data...
February 2017: Aging Cell
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#8
Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
January 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088729/new-insights-into-aox2-transcriptional-regulation-in-chlamydomonas-reinhardtii
#9
Mariya Ostroukhova, Zhanneta Zalutskaya, Elena Ermilova
A feature of the mitochondrial electron transport chain in plants, some protists and many fungi is the presence of two terminal oxidases, the energy-conserving cytochrome oxidase and another termed alternative oxidase (AOX). AOX branches from the main respiratory chain, directly coupling the oxidation of ubiquinol with reduction of oxygen to water. The AOX genes can be divided into two discrete subfamilies, AOX1 and AOX2. Although AOX has been proposed to play essential roles in stress tolerance of organisms, the role of subfamily AOX2 is largely unknown...
December 13, 2016: European Journal of Protistology
https://www.readbyqxmd.com/read/28079887/drp-1-is-required-for-bh3-mimetic-mediated-mitochondrial-fragmentation-and-apoptosis
#10
Mateus Milani, Dominic P Byrne, Georgia Greaves, Michael Butterworth, Gerald M Cohen, Patrick A Eyers, Shankar Varadarajan
The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28078253/effects-of-eicosapentaenoic-acid-and-docosahexaenoic-acid-on-mitochondrial-dna-replication-and-pgc-1%C3%AE-gene-expression-in-c2c12-muscle-cells
#11
Mak-Soon Lee, Yoonjin Shin, Sohee Moon, Seunghae Kim, Yangha Kim
Mitochondrial biogenesis is a complex process requiring coordinated expression of nuclear and mitochondrial genomes. The peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) is a key regulator of mitochondrial biogenesis, and it controls mitochondrial DNA (mtDNA) replication within diverse tissues, including muscle tissue. The aim of this study was to investigate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mtDNA copy number and PGC-1α promoter activity in C2C12 muscle cells...
December 2016: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/28077332/molecular-identification-of-star-and-3%C3%AE-hsd1-and-characterization-in-response-to-gnih-stimulation-in-protogynous-hermaphroditic-grouper-epinephelus-coioides
#12
Qingqing Wang, Xin Qi, Haipei Tang, Yin Guo, Shuisheng Li, Gaofei Li, Xiaoli Yang, Haifa Zhang, Xiaochun Liu, Haoran Lin
Gonadal steroids are critical factors in reproduction and sex reverse process. StAR (steroidogenic acute regulatory protein), transferring the cholesterol from the outer mitochondrial membrane to the inner membrane, is the rate-limiting factor of steroidogenesis. 3βHSD (3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase), converting Δ5-steroids into Δ4-steroids, is an important oxidoreductase in steroidogenesis. In the present study, StAR and 3βHSD1 were cloned and characterized from protogynous orange-spotted grouper...
January 8, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28077274/the-role-and-regulation-of-the-peroxisome-proliferator-activated-receptor-alpha-in-human-liver
#13
REVIEW
Sander Kersten, Rinke Stienstra
The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver...
January 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28066829/the-multifaceted-role-of-nrf2-in-mitochondrial-function
#14
REVIEW
Kira M Holmström, Rumen V Kostov, Albena T Dinkova-Kostova
The transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the master regulator of the cellular redox homeostasis. Nrf2 target genes comprise of a large network of antioxidant enzymes, proteins involved in xenobiotic detoxification, repair and removal of damaged proteins, inhibition of inflammation, as well as other transcription factors. In recent years it has emerged that as part of its role as a regulator of cytoprotective gene expression, Nrf2 impacts mitochondrial function. Increased Nrf2 activity defends against mitochondrial toxins...
December 2016: Curr Opin Toxicol
https://www.readbyqxmd.com/read/28055010/continued-26s-proteasome-dysfunction-in-mouse-brain-cortical-neurons-impairs-autophagy-and-the-keap1-nrf2-oxidative-defence-pathway
#15
Aslihan Ugun-Klusek, Michael H Tatham, Jamal Elkharaz, Dumitru Constantin-Teodosiu, Karen Lawler, Hala Mohamed, Simon M L Paine, Glen Anderson, R John Mayer, James Lowe, E Ellen Billett, Lynn Bedford
The ubiquitin-proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS and autophagy dysfunctions are believed to have a major role in the pathomechanisms of neurodegenerative disease. Here we show that continued 26S proteasome dysfunction in mouse brain cortical neurons causes paranuclear accumulation of fragmented dysfunctional mitochondria, associated with earlier recruitment of Parkin and lysine 48-linked ubiquitination of mitochondrial outer membrane (MOM) proteins, including Mitofusin-2...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28053575/faba-bean-drought-responsive-gene-identification-and-validation
#16
Megahed H Ammar, Altaf M Khan, Hussein M Migdadi, Samah M Abdelkhalek, Salem S Alghamdi
This study was carried out to identify drought-responsive genes in a drought tolerant faba bean variety (Hassawi 2) using a suppressive subtraction hybridization approach (SSH). A total of 913 differentially expressed clones were sequenced from a differential cDNA library that resulted in a total of 225 differentially expressed ESTs. The genes of mitochondrial and chloroplast origin were removed, and the remaining 137 EST sequences were submitted to the gene bank EST database (LIBEST_028448). A sequence analysis identified 35 potentially drought stress-related ESTs that regulate ion channels, kinases, and energy production and utilization and transcription factors...
January 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28053050/parkin-functionally-interacts-with-pgc-1%C3%AE-to-preserve-mitochondria-and-protect-dopaminergic-neurons
#17
Lu Zheng, Nathalie Bernard-Marissal, Norman Moullan, Davide D'Amico, Johan Auwerx, Darren J Moore, Graham Knott, Patrick Aebischer, Bernard L Schneider
To understand the cause of Parkinson's disease (PD), it is important to determine the functional interactions between factors linked to the disease. Parkin is associated to autosomal recessive early-onset PD, and controls the transcription of PGC-1α, a master regulator of mitochondrial biogenesis. These two factors functionally interact to regulate the turnover and quality of mitochondria, by increasing both mitophagic activity and mitochondria biogenesis. In cortical neurons, co-expressing PGC-1α and Parkin increases the number of mitochondria, enhances maximal respiration, and accelerates the recovery of the mitochondrial membrane potential following mitochondrial uncoupling...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28049732/nadph-oxidase-4-nox4-suppresses-mitochondrial-biogenesis-and-bioenergetics-in-lung-fibroblasts-via-a-nuclear-factor-erythroid-derived-2-like-2-nrf2-dependent-pathway
#18
Karen Bernard, Naomi J Logsdon, Veronica Miguel, Gloria A Benavides, Jianhua Zhang, A Brent Carter, Victor M Darley-Usmar, Victor J Thannickal
Mitochondrial bioenergetics are critical for cellular homeostasis and stress responses. The reactive oxygen species (ROS)-generating enzyme, NADPH oxidase 4 (Nox4), regulates a number of physiological and pathological processes, including cellular differentiation, host defense and tissue fibrosis. In this study, we explored the role of constitutive Nox4 activity in regulating mitochondrial function. An increase in mitochondrial oxygen consumption and reserve capacity was observed in murine and human lung fibroblasts with genetic deficiency (or silencing) of Nox4...
January 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28040472/proatherogenic-effects-of-4-hydroxynonenal
#19
Anne Nègre-Salvayre, Sandra Garoby-Salom, Audrey Swiader, Myriam Rouahi, Mélanie Pucelle, Robert Salvayre
4-hydroxy-2-nonenal (HNE) is a α,β-unsaturated hydroxyalkenal generated by peroxidation of n-6 polyunsaturated fatty acid. This reactive carbonyl compound exhibits a huge number of biological properties that result mainly from the formation of HNE-adducts on free amino groups and thiol groups in proteins. In the vascular system, HNE adduct accumulation progressively leads to cellular dysfunction and tissue damages that are involved in the progression of atherosclerosis and related diseases. HNE contributes to the atherogenicity of oxidized LDL, by forming HNE-apoB adducts that deviate the LDL metabolism to the scavenger receptor pathway of macrophagic cells, and lead to the formation of foam cells...
December 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28039408/nrf2-deficiency-does-not-affect-denervation-induced-alterations-in-mitochondrial-fission-and-fusion-proteins-in-skeletal-muscle
#20
Yu Kitaoka, Kohei Takeda, Yuki Tamura, Shin Fujimaki, Tohru Takemasa, Hideo Hatta
Oxidative stress-induced mitochondrial dysfunction is associated with age-related and disuse-induced skeletal muscle atrophy. However, the role of nuclear factor erythroid 2-related factor 2 (Nrf2) during muscle fiber atrophy remains to be elucidated. In this study, we examined whether deficiency of Nrf2, a master regulator of antioxidant transcription, promotes denervation-induced mitochondrial fragmentation and muscle atrophy. We found that the expression of Nrf2 and its target antioxidant genes was upregulated at 2 weeks after denervation in wild-type (WT) mice...
December 2016: Physiological Reports
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