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https://www.readbyqxmd.com/read/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#1
Oihane Erice, Patricia Munoz-Garrido, Javier Vaquero, Maria J Perugorria, Maite G Fernandez-Barrena, Elena Saez, Alvaro Santos-Laso, Ander Arbelaiz, Raul Jimenez-Agüero, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P Oude Elferink, Nicholas F LaRusso, Luis Bujanda, Jose J G Marin, Jesus M Banales
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase complex-E2 (PDC-E2) is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but their functional relevance is largely unknown. We previously reported that miR-506 is overexpressed in PBC cholangiocytes and directly targets both Cl(-) /HCO3(-) anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor (InsP3R3), leading to cholestasis...
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28920396/-inhibition-of-chitin-oligosaccharide-on-dyslipidemia-and-the-potential-molecular-mechanism-exploration
#2
Fanqi Yi, Junping Zheng, Qiongyu Li, Siming Jiao, Yuguang Du, Yun Ye, Hongtao Liu
The inhibitory effect of NACOS on dyslipidemia and potential molecular mechanisms by in vitro and in vivo experiments were investigated. For in vitro study, four experimental groups were designed by using HepG2 cells, including the control group, palmitic acid (PA) treatment alone group, NACOS treatment alone group and NACOS + PA treatment group. For in vivo study, male C57BL/6 mice were divided into four groups (n=5) at random including the normal control group (NCD), high fat diet (HFD) group, NACOS treatment alone group, NACOS+HFD group, which were treated for 20 weeks...
April 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28919908/hepatic-s6k1-partially-regulates-lifespan-of-mice-with-mitochondrial-complex-i-deficiency
#3
Takashi K Ito, Chenhao Lu, Jacob Khan, Quy Nguyen, Heather Z Huang, Dayae Kim, James Phillips, Jo Tan, Yenna Lee, Tuyet Nguyen, Samy Khessib, Natalie Lim, Surapat Mekvanich, Joshua Oh, Victor V Pineda, Weirong Wang, Alessandro Bitto, Jonathan Y An, John F Morton, Mitsutoshi Setou, Warren C Ladiges, Matt Kaeberlein
The inactivation of ribosomal protein S6 kinase 1 (S6K1) recapitulates aspects of caloric restriction and mTORC1 inhibition to achieve prolonged longevity in invertebrate and mouse models. In addition to delaying normative aging, inhibition of mTORC1 extends the shortened lifespan of yeast, fly, and mouse models with severe mitochondrial disease. Here we tested whether disruption of S6K1 can recapitulate the beneficial effects of mTORC1 inhibition in the Ndufs4 knockout (NKO) mouse model of Leigh Syndrome caused by Complex I deficiency...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28919865/coping-with-salt-water-habitats-metabolic-and-oxidative-responses-to-salt-intake-in-the-rufous-collared-sparrow
#4
Pablo Sabat, Cristóbal Narváez, Isaac Peña-Villalobos, Carolina Contreras, Karin Maldonado, Juan C Sanchez-Hernandez, Seth D Newsome, Roberto Nespolo, Francisco Bozinovic
Many physiological adjustments occur in response to salt intake in several marine taxa, which manifest at different scales from changes in the concentration of individual molecules to physical traits of whole organisms. Little is known about the influence of salinity on the distribution, physiological performance, and ecology of passerines; specifically, the impact of drinking water salinity on the oxidative status of birds has been largely ignored. In this study, we evaluated whether experimental variations in the salt intake of a widely-distributed passerine (Zontotrichia capensis) could generate differences in basal (BMR) and maximum metabolic rates (Msum), as well as affect metabolic enzyme activity and oxidative status...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28918598/triacsin-c-reduces-lipid-droplet-formation-and-induces-mitochondrial-biogenesis-in-primary-rat-hepatocytes
#5
Carlos R P Dechandt, Felippe H Zuccolotto-Dos-Reis, Bruno G Teodoro, Anna Maria A P Fernandes, Marcos N Eberlin, Isis C Kettelhut, Carlos Curti, Luciane C Alberici
Intracellular long-chain acyl-CoA synthetases (ACSL) activate fatty acids to produce acyl-CoA, which undergoes β-oxidation and participates in the synthesis of esterified lipids such as triacylglycerol (TAG). Imbalances in these metabolic routes are closely associated with the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Triacsin C is one of the few compounds that inhibit TAG accumulation into lipid droplets (LD) by suppressing ACSL activity. Here we report that treatment of primary rat hepatocytes with triacsin C at concentrations lower than the IC50 (4...
September 16, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28916388/differential-effects-of-fxr-or-tgr5-activation-in-cholangiocarcinoma-progression
#6
O Erice, I Labiano, A Arbelaiz, A Santos-Laso, P Munoz-Garrido, R Jimenez-Agüero, P Olaizola, A Caro-Maldonado, N Martín-Martín, A Carracedo, E Lozano, J J Marin, C J O'Rourke, J B Andersen, J Llop, V Gómez-Vallejo, D Padro, A Martin, M Marzioni, L Adorini, M Trauner, L Bujanda, M J Perugorria, J M Banales
BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines...
September 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28914762/the-1-week-and-8-month-effects-of-a-ketogenic-diet-or-ketone-salt-supplementation-on-multi-organ-markers-of-oxidative-stress-and-mitochondrial-function-in-rats
#7
Wesley C Kephart, Petey W Mumford, Xuansong Mao, Matthew A Romero, Hayden W Hyatt, Yufeng Zhang, Christopher B Mobley, John C Quindry, Kaelin C Young, Darren T Beck, Jeffrey S Martin, Danielle J McCullough, Dominic P D'Agostino, Ryan P Lowery, Jacob M Wilson, Andreas N Kavazis, Michael D Roberts
We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses...
September 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28912098/melatonin-mediated-upregulation-of-sirt3-attenuates-sodium-fluoride-induced-hepatotoxicity-by-activating-the-mt1-pi3k-akt-pgc-1%C3%AE-signaling-pathway
#8
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
September 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28911986/virtual-cell-based-assay-simulation-of-intra-mitochondrial-concentration-in-hepatocytes-and-cardiomyocytes
#9
Andrew P Worth, Jochem Louisse, Peter Macko, Jose Vicente Sala Benito, Alicia Paini
In order to replace the use of animals in toxicity testing, there is a need to predict human in vivo toxic doses from concentrations that cause adverse effects in in vitro test systems. The virtual cell based assay (VCBA) has been developed to simulate intracellular concentrations as a function of time, and can be used to interpret in vitro concentration-response curves. In this study we refine and extend the VCBA model by including additional target-organ cell models and by simulating the fate and effects of chemicals at the organelle level...
September 11, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28906435/mitochondrial-biogenesis-in-response-to-chromium-vi-toxicity-in-human-liver-cells
#10
Xiali Zhong, Rita de Cássia da Silveira E Sá, Caigao Zhong
Hexavalent chromium (Cr(VI)) is a ubiquitous environmental pollutant, which poses a threat to human public health. Recent studies have shown that mitochondrial biogenesis can be activated by inflammatory and oxidative stress. However, whether mitochondrial biogenesis is involved in Cr(VI)-induced hepatotoxicity is unclear. Here, we demonstrated the induction of inflammatory response and oxidative stress, as indicated by upregulation of inflammatory factors and reactive oxygen species (ROS). Subsequently, we demonstrated that mitochondrial biogenesis, comprising the mitochondrial DNA copy number and mitochondrial mass, was significantly increased in HepG2 cells exposed to low concentrations of Cr(VI)...
September 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28905505/biallelic-variants-in-wars2-encoding-mitochondrial-tryptophanyl-trna-synthase-in-six-individuals-with-mitochondrial-encephalopathy
#11
Saskia B Wortmann, Sharita Timal, Hanka Venselaar, Liesbeth T Wintjes, Robert Kopajtich, René G Feichtinger, Carla Onnekink, Mareike Mühlmeister, Ulrich Brandt, Jan A Smeitink, Joris A Veltman, Wolfgang Sperl, Dirk Lefeber, Ger Pruijn, Vesna Stojanovic, Peter Freisinger, Francjan V Spronsen, Terry Gj Derks, Hermine E Veenstra-Knol, Johannes A Mayr, Agnes Rötig, Mark Tarnopolsky, Holger Prokisch, Richard J Rodenburg
Mitochondrial protein synthesis involves an intricate interplay between mitochondrial DNA encoded RNAs and nuclear DNA encoded proteins, such as ribosomal proteins and aminoacyl-tRNA synthases. Eukaryotic cells contain 17 mitochondria-specific aminoacyl-tRNA synthases. WARS2 encodes mitochondrial tryptophanyl-tRNA synthase (mtTrpRS), a homodimeric class Ic enzyme (mitochondrial tryptophan-tRNA ligase; EC 6.1.1.2). Here, we report six individuals from five families presenting with either severe neonatal onset lactic acidosis, encephalomyopathy and early death or a later onset, more attenuated course of disease with predominating intellectual disability...
September 14, 2017: Human Mutation
https://www.readbyqxmd.com/read/28903946/ppara-agonist-fenofibrate-enhances-fatty-acid-%C3%AE-oxidation-and-attenuates-polycystic-kidney-and-liver-disease-in-mice
#12
Ronak Lakhia, Matanel Yheskel, Andrea Flaten, Ezekiel B Quittner-Strom, William L Holland, Vishal Patel
PPARA is nuclear hormone receptor that promotes fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS). We and others have recently shown that PPARA and its target genes are downregulated, and FAO and OXPHOS are impaired in autosomal dominant polycystic kidney disease (ADPKD). However, whether PPARA and FAO/OXPHOS are causally linked to ADPKD progression is not entirely clear. We report that expression of PPARA and FAO/OXPHOS genes is downregulated and in-vivo β-oxidation rate of 3H-labelled triolein is reduced in Pkd1RC/RC mice, a slowly-progressing orthologous model of ADPKD that closely mimics the human ADPKD phenotype...
September 13, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28903497/downregulation-of-tmem70-in-rat-liver-cells-after-hepatocarcinogen-treatment-related-to-the-warburg-effect-in-hepatocarcinogenesis-producing-gst-p-expressing-proliferative-lesions
#13
Sayaka Mizukami, Yousuke Watanabe, Kota Nakajima, Yasuko Hasegawa-Baba, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
We previously observed downregulation of mitochondrial oxidative phosphorylation-related protein, TMEM70, which is suggestive of disrupted cellular senescence, in GST-P-expressing (+) proliferative lesions from early hepatocarcinogenesis stages in rats. The present study investigated the immunohistochemical relationship between TMEM70 downregulation and cellular metabolic changes in carcinogenic processes, as well as the onset of the liver cell respiratory changes after repeated hepatocarcinogen treatment in rats...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28902430/reduced-serum-igf-1-associated-with-hepatic-osteodystrophy-is-a-main-determinant-of-low-cortical-but-not-trabecular-bone-mass
#14
Zhongbo Liu, Tianzhen Han, Haim Werner, Clifford J Rosen, Mitchell B Schaffler, Shoshana Yakar
Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO)...
September 13, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28900784/liver-involvement-in-urea-cycle-disorders-a-review-of-the-literature
#15
REVIEW
Adrien Bigot, Michel C Tchan, Benjamin Thoreau, Hélène Blasco, François Maillot
Urea cycle disorders (UCDs) are inborn errors of metabolism of the nitrogen detoxification pathway and encompass six principal enzymatic deficiencies. The aging of UCD patients leads to a better knowledge of the long-term natural history of the condition and to the reporting of previously unnoticed manifestations. Despite historical evidence of liver involvement in UCDs, little attention has been paid to this organ until recently. Hence, we reviewed the available scientific evidence on acute and chronic liver dysfunction and liver carcinogenesis in UCDs and discuss their pathophysiology...
September 12, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28900305/berberine-ameliorates-fatty-acid-induced-oxidative-stress-in-human-hepatoma-cells
#16
Yixuan Sun, Xinlu Yuan, Feifei Zhang, Yamei Han, Xinxia Chang, Xi Xu, Yu Li, Xin Gao
Oxidative stress is thought to be critical for the pathogenesis of hepatic steatosis and its progress to non-alcoholic steatohepatitis. Berberine (BBR) can improve hepatic steatosis. In this study, we investigated the role of BBR in ameliorating oxidative stress. Lipid accumulation was measured in the livers of C57BL/6 mice fed a high fat diet (HFD) or a normal diet for 8 weeks, then either received BBR or vehicle for the study duration. Nrf2 distribution was detected in male Sprague-Dawley rats' livers in vivo and in Huh7 cells in vitro...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900165/gcn5l1-modulates-cross-talk-between-mitochondria-and-cell-signaling-to-regulate-foxo1-stability-and-gluconeogenesis
#17
Lingdi Wang, Iain Scott, Lu Zhu, Kaiyuan Wu, Kim Han, Yong Chen, Marjan Gucek, Michael N Sack
The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation...
September 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28899382/carrion-crows-corvus-corone-of-southwest-germany-important-hosts-for-haemosporidian-parasites
#18
Sandrine Schmid, Katrin Fachet, Anke Dinkel, Ute Mackenstedt, Friederike Woog
BACKGROUND: Avian malaria parasites (Plasmodium spp.) and other Haemosporida (Haemoproteus and Leucocytozoon spp.) form a diverse group of vector-transmitted blood parasites that are abundant in many bird families. Recent studies have suggested that corvids may be an important host for Plasmodium spp. and Leucocytozoon spp. METHODS: To investigate the diversity of Haemosporida of resident carrion crows (Corvus corone) and Eurasian Magpies (Pica pica) in southwest Germany, 100 liver samples of corvids were examined using a nested PCR method to amplify a 1063 bp fragment of the haemosporidian mitochondrial cytochrome b gene...
September 12, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28898446/contradictory-effects-of-mitochondria-and-non-mitochondria-targeted-antioxidants-on-hepatocarcinogenesis-by-altering-dna-repair
#19
Bibo Wang, Jing Fu, Ting Yu, An Xu, Wenhao Qin, Zhishi Yang, Yao Chen, Hongyang Wang
Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, it does not fully deny antioxidants for cancer prevention. Both tumor and antioxidants types influence the actual efficacy. However, little is known about the impact of different types of antioxidants on primary hepatocellular carcinoma (HCC), including non-mitochondrial- and mitochondrial-targeted antioxidants...
September 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28894435/neuroactive-steroids-receptor-interactions-and-responses
#20
REVIEW
Kald Beshir Tuem, Tesfay Mehari Atey
Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors...
2017: Frontiers in Neurology
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