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Liver mitochondria

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https://www.readbyqxmd.com/read/28934226/pathological-alterations-in-liver-injury-following-congestive-heart-failure-induced-by-volume-overload-in-rats
#1
Mohammed Shaqura, Doaa M Mohamed, Noureddin B Aboryag, Lama Bedewi, Lukas Dehe, Sascha Treskatsch, Mehdi Shakibaei, Michael Schäfer, Shaaban A Mousa
Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors...
2017: PloS One
https://www.readbyqxmd.com/read/28931544/a-mitohormetic-response-to-pro-oxidant-exposure-in-the-house-mouse
#2
Yufeng Zhang, Frances Humes, Gregory Almond, Andreas N Kavazis, Wendy R Hood
Mitochondria are hypothesized to display a biphasic response to reactive oxygen species (ROS) exposure. In this study, we evaluated the time course changes in mitochondrial performance and oxidative stress in house mice following X-irradiation. Forty-eight mice were equally divided among six groups, including a non-irradiated control and 5 experimental groups that varied in time between X-ray exposure and euthanasia (1 hour, 1, 4, 7, or 10 days after X-irradiation). We measured parameters associated with mitochondrial respiratory function and ROS emission from isolated liver and skeletal muscle mitochondria and levels of oxidative damage and antioxidants in liver, skeletal muscle, and heart tissues...
September 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28930172/rhein-induces-oxidative-stress-and-apoptosis-in-mouse-blastocysts-and-has-immunotoxic-effects-during-embryonic-development
#3
Chien-Hsun Huang, Wen-Hsiung Chan
Rhein, a glucoside chemical compound found in a traditional Chinese medicine derived from the roots of rhubarb, induces cell apoptosis and is considered to have high potential as an antitumor drug. Several previous studies showed that rhein can inhibit cell proliferation and trigger mitochondria-related or endoplasmic reticulum (ER) stress-dependent apoptotic processes. However, the side effects of rhein on pre- and post-implantation embryonic development remain unclear. Here, we show that rhein has cytotoxic effects on blastocyst-stage mouse embryos and induces oxidative stress and immunotoxicity in mouse fetuses...
September 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28925474/mitochondrial-protein-ucp1-mediates-liver-injury-induced-by-lps-through-ekr-signaling-pathway
#4
P Liu, J Yang, Z-Y Chen, P Zhang, G-J Shi
OBJECTIVE: Mitochondria are abundant in liver. The roles of mitochondrial protein in liver injury and related signaling pathways are still unclear. UCP1 is a novel mitochondrial transmembrane protein. Its expression pattern and function in liver still needs further investigation. MATERIALS AND METHODS: A mouse model of liver injury was established by the treatment of LPS. UCP1 expression in the liver tissue was detected by Western blot and qRT-PCR. ERK signaling activity was tested by enzymatic activity kit...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28923495/crispr-cas9-engineering-of-adult-mouse-liver-demonstrates-that-the-dnajb1-prkaca-gene-fusion-is-sufficient-to-induce-tumors-resembling-fibrolamellar-hepatocellular-carcinoma
#5
Lars H Engelholm, Anjum Riaz, Denise Serra, Frederik Dagnæs-Hansen, Jens V Johansen, Eric Santoni-Rugiu, Steen H Hansen, Francesco Niola, Morten Frödin
BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28923347/sulforaphane-improves-disrupted-er-mitochondria-interactions-and-suppresses-exaggerated-hepatic-glucose-production
#6
Emily Tubbs, Annika S Axelsson, Guillaume Vial, Claes B Wollheim, Jennifer Reuisset, Anders H Rosengren
AIMS: Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs...
September 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#7
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/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#8
Cliff Rowe, Mohsen Shaeri, Emma Large, Terri Cornforth, Angela Robinson, Tomasz Kostrzewski, Rowena Sison-Young, Christopher Goldring, Kevin Park, David Hughes
Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28918598/triacsin-c-reduces-lipid-droplet-formation-and-induces-mitochondrial-biogenesis-in-primary-rat-hepatocytes
#9
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/28915639/heptamethine-carbocyanine-dz-1-dye-for-near-infrared-fluorescence-imaging-of-hepatocellular-carcinoma
#10
Jiaze An, Ningning Zhao, Caiqin Zhang, Yong Zhao, Dengxu Tan, Ya Zhao, Bing Bai, Hai Zhang, Boyang Jason Wu, Changhong Shi
Near-infrared fluorescence (NIRF) dyes have recently emerged as promising tools for non-invasive imaging of different types of cancers. Here, we explored the potential utility of a NIRF DZ-1 dye, with dual imaging and tumour targeting functions, in hepatocellular carcinoma (HCC). We showed the preferential uptake of DZ-1 by HCC cells in vitro and in derived subcutaneous/orthotopic tumour xenografts, accompanied by a minimal effect on normal cells. DZ-1 simplified tumour growth profiling as well, since we were able to correlate NIRF signals with tumour volume and/or tumour-emitting luminescence in mice...
August 22, 2017: Oncotarget
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
#11
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/28905505/biallelic-variants-in-wars2-encoding-mitochondrial-tryptophanyl-trna-synthase-in-six-individuals-with-mitochondrial-encephalopathy
#12
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/28900165/gcn5l1-modulates-cross-talk-between-mitochondria-and-cell-signaling-to-regulate-foxo1-stability-and-gluconeogenesis
#13
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/28898446/contradictory-effects-of-mitochondria-and-non-mitochondria-targeted-antioxidants-on-hepatocarcinogenesis-by-altering-dna-repair
#14
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/28889276/thallium-toxicity-general-issues-neurological-symptoms-and-neurotoxic-mechanisms
#15
Laura Osorio-Rico, Abel Santamaria, Sonia Galván-Arzate
Thallium (Tl(+)) is a ubiquitous natural trace metal considered as the most toxic among heavy metals. The ionic ratio of Tl(+) is similar to that of potassium (K(+)), therefore accounting for the replacement of the latter during enzymatic reactions. The principal organelle damaged after Tl(+) exposure is mitochondria. Studies on the mechanisms of Tl(+) include intrinsic pathways altered and changes in antiapoptotic and proapoptotic proteins, cytochrome c, and caspases. Oxidative damage pathways increase after Tl(+) exposure to produce reactive oxygen species (ROS), changes in physical properties of the cell membrane caused by lipid peroxidation, and concomitant activation of antioxidant mechanisms...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28880749/exposure-to-decabromodiphenyl-ether-bde-209-produces-mitochondrial-dysfunction-in-rat-liver-and-cell-death
#16
Lilian C Pereira, Alecsandra O Souza, Maria J Tasso, Alana M C Oliveira, Filipe V Duarte, Carlos M Palmeira, Daniel J Dorta
Polybrominated diphenyl ethers (PBDE) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunctions, reproductive disorders, and hepatotoxicity. The widespread use of PBDE as flame retardants has culminated in daily exposure of humans and wildlife to these contaminants and resulted in their banned use. Thus assessment of the potential effects of each PBDE congener on living organisms has become cause for concern. The aim of this study was to (1) examine the effects of decabromodiphenyl ether (BDE)-209 on different functions of HepG2 cells and (2) investigate whether this congener is involved in mitochondrial toxicity...
September 7, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28878165/mitochondrial-liver-toxicity-of-valproic-acid-and-its-acid-derivatives-is-related-to-inhibition-of-945-lipoamide-dehydrogenase
#17
Alexei P Kudin, Hafiz Mawasi, Arik Eisenkraft, Christian E Elger, Meir Bialer, Wolfram S Kunz
The liver toxicity of valproic acid (VPA) is an established side effect of this widely used antiepileptic drug, which is extremely problematic for patients with metabolic epilepsy and particularly epilepsy due to mitochondrial dysfunction. In the present report, we investigated the reason for liver mitochondrial toxicity of VPA and several acid and amide VPA analogues. While the pyruvate and 2-oxoglutarate oxidation rates of rat brain mitochondria were nearly unaffected by VPA, rat liver mitochondrial pyruvate and 2-oxoglutarate oxidation was severely impaired by VPA concentrations above 100 µM...
September 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28870272/in-rats-gestational-iron-deficiency-does-not-change-body-fat-or-hepatic-mitochondria-in-the-aged-offspring
#18
W D Rees, S M Hay, H E Hayes, C Birgovan, H J McArdle
Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks...
September 5, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28861173/therapeutic-effect-of-rosuvastatin-and-propylthiouracil-on-ameliorating-high-cholesterol-diet-induced-fatty-liver-disease-fibrosis-and-inflammation-in-rabbit
#19
Pao-Yuan Lin, Chih-Hung Chen, Christopher Glenn Wallace, Kuan-Hung Chen, Chia-Lo Chang, Hong-Hwa Chen, Pei-Hsun Sung, Kun-Chen Lin, Sheung-Fat Ko, Cheuk-Kwan Sun, Hsueh-Wen Chang, Pei-Lin Shao, Mel S Lee, Hon-Kan Yip
This study tested the hypothesis that high-cholesterol diet (HCD)-induced fatty liver disease could be ameliorated by rosuvastatin (Ros) and propylthiouracil (PTU) therapy. Thirty-two Zealand rabbits were equally divided into group 1 (sham-control), group 2 (HCD for 8 weeks), group 3 [HCD-Ros (20 mg/kg/day administration after 4-week HFD for 4 weeks)], group 4 [HCD-PTU (0.1% PTU in drinking water) with treatment course as group 3]. Liver weight, fibrosis, collagen deposition area, and serum levels of AST/ALT were highest in group 2, lowest in group 1, and significantly higher in group 4 than group 3 (all P<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28844938/amc-bio-artificial-liver-culturing-enhances-mitochondrial-biogenesis-in-human-liver-cell-lines-the-role-of-oxygen-medium-perfusion-and-3d-configuration
#20
Aziza A A Adam, Martien van Wenum, Vincent A van der Mark, Aldo Jongejan, Perry D Moerland, Riekelt H Houtkooper, Ronald J A Wanders, Ronald P Oude Elferink, Robert A F M Chamuleau, Ruurdtje Hoekstra
BACKGROUND: Human liver cell lines, like HepaRG and C3A, acquire higher functionality when cultured in the AMC-Bio-Artificial Liver (AMC-BAL). The three main differences between BAL and monolayer culture are the oxygenation (40% vs 20%O2), dynamic vs absent medium perfusion and 3D vs 2D configuration. Here, we investigated the background of the differences between BAL-cultures and monolayers. METHODS: We performed whole-genome microarray analysis on HepaRG monolayer and BAL-cultures...
August 24, 2017: Mitochondrion
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