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https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#1
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29145655/paternal-exposure-to-environmental-chemical-stress-affectsmale-offspring-s-hepatic-mitochondria
#2
Roger Godschalk, Alex Remels, Camiel Hoogendoorn, Jan van Benthem, Mirjam Luijten, Nur Duale, Gunnar Brunborg, Ann-Karin Olsen, Freek G Bouwman, Armelle Munnia, Marco Peluso, Edwin Mariman, Frederik Jan van Schooten
Pre-conceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3x per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29145424/levosimendan-protects-human-hepatocytes-from-ischemia-reperfusion-injury
#3
Stefanie N Brunner, Nicolai V Bogert, Andreas A Schnitzbauer, Eva Juengel, Anton Moritz, Isabella Werner, Angela Kornberger, Andres Beiras-Fernandez
BACKGROUND: Ischemia-reperfusion injury (IRI) is a major challenge in liver transplantation. The mitochondrial pathway plays a pivotal role in hepatic IRI. Levosimendan, a calcium channel sensitizer, was shown to attenuate apoptosis after IRI in animal livers. The aim of this study was to investigate the effect of levosimendan on apoptosis in human hepatocytes. METHODS: Primary human hepatocytes were either exposed to hypoxia or cultured under normoxic conditions...
2017: PloS One
https://www.readbyqxmd.com/read/29143783/metformin-potentiates-the-benefits-of-dietary-restraint-a-metabolomic-study
#4
Marta Riera-Borrull, Anabel García-Heredia, Salvador Fernández-Arroyo, Anna Hernández-Aguilera, Noemí Cabré, Elisabet Cuyàs, Fedra Luciano-Mateo, Jordi Camps, Javier A Menendez, Jorge Joven
Prevention of the metabolic consequences of a chronic energy-dense/high-fat diet (HFD) represents a public health priority. Metformin is a strong candidate to be incorporated in alternative therapeutic approaches. We used a targeted metabolomic approach to assess changes related to the multi-faceted metabolic disturbances provoked by HFD. We evaluated the protective effects of metformin and explored how pro-inflammatory and metabolic changes respond when mice rendered obese, glucose-intolerant and hyperlipidemic were switched to diet reversal with or without metformin...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29141573/liver-protective-effects-of-extra-virgin-olive-oil-interaction-between-its-chemical-composition-and-the-cell-signaling-pathways-involved-in-protection
#5
Sandra A Soto-Alarcon, Rodrigo Valenzuela, Alfonso Valenzuela, Luis A Videla
BACKGROUND AND OBJECTIVE: The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage...
November 14, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29141243/trolline-ameliorates-liver-fibrosis-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway-promoting-hsc-apoptosis-and-suppressing-autophagy
#6
Facheng Bai, Quanfang Huang, Jinlan Nie, Shengjuan Lu, Chunyuan Lu, Xunshuai Zhu, Yuxin Wang, Lang Zhuo, Zhongpeng Lu, Xing Lin
BACKGROUND/AIMS: Previous studies have shown that trolline possesses various forms of pharmacological activity, including antibacterial and antiviral potency. The present paper addressed the putative hepatoprotective effects of trolline. METHODS: Rats received 2 ml/kg CCl4 (mixed 1: 1 in peanut oil) intragastrically twice a week for 8 weeks to induce hepatic fibrosis. The animals were then treated with trolline for additional 4 weeks. Liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29138968/mitochondrial-dysfunctions-contribute-to-energy-deficits-in-rodent-model-of-hepatic-encephalopathy
#7
Saurabh Dhanda, Aditya Sunkaria, Avishek Halder, Rajat Sandhir
Perturbations in the cerebral energy metabolism are anticipated to be an important factor by which ammonia may exert its toxic effects on the central nervous system. The present study was designed to investigate the role of impaired mitochondrial functions and cerebral energy metabolism in the development hepatic encephalopathy (HE) induced by of bile duct ligation (BDL). After four weeks of BDL, a significant increase in hepatic hydroxyproline and collagen content was observed which confirmed biliary fibrosis...
November 14, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29132413/germacranolide-type-sesquiterpene-lactones-from-smallanthus-sonchifolius-with-promising-activity-against-leishmania-mexicana-and-trypanosoma-cruzi
#8
Jerónimo L Ulloa, Renata Spina, Agustina Casasco, Patricia B Petray, Virginia Martino, Miguel A Sosa, Fernanda M Frank, Liliana V Muschietti
BACKGROUND: Leishmaniasis and Chagas disease are life-threatening illnesses caused by the protozoan parasites Leishmania spp. and Trypanosoma cruzi, respectively. They are known as "neglected diseases" due to the lack of effective drug treatments and the scarcity of research work devoted to them. Therefore, the development of novel and effective drugs is an important and urgent need. Natural products are an important source of bioactive molecules for the development of new drugs. In this study, we evaluated the activity of enhydrin, uvedalin and polymatin B, three sesquiterpene lactones (STLs) isolated from Smallanthus sonchifolius, on Leishmania mexicana (MNYC/BZ/62/M) and Trypanosoma cruzi (Dm28c)...
November 13, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29129519/sirt6-protects-against-hepatic-ischemia-reperfusion-injury-by-inhibiting-apoptosis-and-autophagy-related-cell-death
#9
Song Zhang, Shuai Jiang, Haiping Wang, Wencheng Di, Chao Deng, Zhenxiao Jin, Wei Yi, Xiao Xiao, Yongzhan Nie, Yang Yang
Silent information regulator 6 (SIRT6), a class III histone deacetylase, has been revealed to participate in multiple metabolic processes in the liver, and it plays important roles in protecting against ischemia/reperfusion (I/R) injury in multiple organs. In this study, we explored whether SIRT6 is protective against hepatic I/R injury and elucidated the underlying mechanisms. The expression of SIRT6 was significantly decreased during reperfusion compared with the control group. SIRT6-LKO mice exhibited significantly aggravated oxidative stress, mitochondrial dysfunction, inflammatory responses, mitogen-activated protein kinase (MAPK) signaling activation, and apoptosis and autophagy related hepatocyte death compared with control mice...
November 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29128212/liver-proteomic-analysis-of-postpartum-holstein-cows-exposed-to-heat-stress-or-cooling-conditions-during-the-dry-period
#10
Amy L Skibiel, Maya Zachut, Bruno C do Amaral, Yishai Levin, Geoffrey E Dahl
Heat stress negatively affects cow performance, compromises immune function, and increases susceptibility to metabolic disorders, particularly during the dry period and as cows transition from gestation to lactation. Metabolic adaptations of the liver are critical for successful transition, yet it is unclear how heat stress affects metabolic pathways within the liver at the proteomic level. The objective of this study was to investigate the liver proteome of postpartum cows that were cooled or heat stressed during the dry period to gain insight into how protein expression is altered by prior heat stress and may contribute to performance and disease outcomes...
November 8, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29127360/a-mouse-model-of-autoimmune-cholangitis-via-syngeneic-bile-duct-protein-immunization
#11
Wen-Tao Ma, Qing-Zhi Liu, Jing-Bo Yang, Yan-Qing Yang, Zhi-Bin Zhao, Hong-Di Ma, M Eric Gershwin, Zhe-Xiong Lian
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the destruction of interlobular biliary ductules, which progressively leads to cholestasis, hepatic fibrosis, cirrhosis, and eventually liver failure. Several mouse models have been used to clarify the pathogenesis of PBC and are generally considered reflective of an autoimmune cholangitis. Most models focus on issues of molecular mimicry between the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC and xenobiotic cross reactive chemicals...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119002/mechanisms-of-liver-disease-in-patients-infected-with-hiv
#12
REVIEW
Matthew B Kaspar, Richard K Sterling
Objective: To describe the various mechanisms of liver disease in patients with HIV infection, and to link these mechanisms to disease states which may utilise them. Background: Non-AIDS causes of morbidity and mortality are becoming increasingly common in patients chronically infected with HIV. In particular, liver-related diseases have risen to become one of the leading causes of non-AIDS-related death. A thorough understanding of the mechanisms driving the development of liver disease in these patients is essential when evaluating and caring for these patients...
2017: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/29116185/targeted-metabolomics-reveals-abnormal-hepatic-energy-metabolism-by-depletion-of-%C3%AE-carotene-oxygenase-2-in-mice
#13
Lei Wu, Xin Guo, Yi Lyu, Stephen L Clarke, Edralin A Lucas, Brenda J Smith, Deana Hildebrand, Weiqun Wang, Denis M Medeiros, Xinchun Shen, Dingbo Lin
β-carotene oxygenase 2 (BCO2) is a carotenoid cleavage enzyme located in the inner mitochondrial membrane. Ablation of BCO2 impairs mitochondrial function leading to oxidative stress. Herein, we performed a targeted metabolomics study using ultrahigh performance liquid chromatography-tandem mass spectroscopy and gas chromatography-mass spectroscopy to discriminate global metabolites profiles in liver samples from six-week-old male BCO2 systemic knockout (KO), heterozygous (Het), and wild type (WT) mice fed a chow diet...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109438/vsig4-inhibits-proinflammatory-macrophage-activation-by-reprogramming-mitochondrial-pyruvate-metabolism
#14
Jialin Li, Bo Diao, Sheng Guo, Xiaoyong Huang, Chengying Yang, Zeqing Feng, Weiming Yan, Qin Ning, Lixin Zheng, Yongwen Chen, Yuzhang Wu
Exacerbation of macrophage-mediated inflammation contributes to pathogenesis of various inflammatory diseases, but the immunometabolic programs underlying regulation of macrophage activation are unclear. Here we show that V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein that is expressed by resting macrophages, inhibits macrophage activation in response to lipopolysaccharide. Vsig4 (-/-) mice are susceptible to high-fat diet-caused obesity and murine hepatitis virus strain-3 (MHV-3)-induced fulminant hepatitis due to excessive macrophage-dependent inflammation...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29107792/caffeine-and-acetaminophen-association-effects-on-mitochondrial-bioenergetics
#15
Débora F Gonçalves, Nelson R de Carvalho, Martim B Leite, Aline A Courtes, Diane D Hartmann, Sílvio T Stefanello, Ingrid K da Silva, Jéferson L Franco, Félix A A Soares, Cristiane L Dalla Corte
AIMS: Many studies have been demonstrating the role of mitochondrial function in acetaminophen (APAP) hepatotoxicity. Since APAP is commonly consumed with caffeine, this work evaluated the effects of the combination of APAP and caffeine on hepatic mitochondrial bioenergetic function in mice. MAIN METHODS: Mice were treated with caffeine (20mg/kg, intraperitoneal (i.p.)) or its vehicle and, after 30min, APAP (250mg/kg, i.p.) or its vehicle. Four hours later, livers were removed, and the parameters associated with mitochondrial function and oxidative stress were evaluated...
October 28, 2017: Life Sciences
https://www.readbyqxmd.com/read/29107739/comparative-restoration-of-acute-liver-failure-by-menstrual-blood-stem-cells-compared-with-bone-marrow-stem-cells-in-mice-model
#16
Mina Fathi-Kazerooni, Gholamreza Tavoosidana, Masoud Taghizadeh-Jahed, Sayeh Khanjani, Hananeh Golshahi, Caroline E Gargett, Haleh Edalatkhah, Somaieh Kazemnejad
BACKGROUND AIMS: The application of menstrual blood stem cells (MenSCs) in regenerative medicine is gaining increasing attention. The aim of this study was to investigate the therapeutic potential of MenSCs compared with bone marrow-derived stem cells (BMSCs) in an animal model of CCl4-induced acute hepatic failure. METHODS: Injured Balb/C mice were divided into multiple groups and received MenSCs, BMSCs or hepatocyte progenitor-like (HPL) cells derived from these cells...
October 26, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29107293/the-mitochondrial-pyruvate-carrier-mediates-high-fat-diet-induced-increases-in-hepatic-tca-cycle-capacity
#17
Adam J Rauckhorst, Lawrence R Gray, Ryan D Sheldon, Xiaorong Fu, Alvin D Pewa, Charlotte R Feddersen, Adam J Dupuy, Katherine N Gibson-Corley, James E Cox, Shawn C Burgess, Eric B Taylor
OBJECTIVE: Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#18
Wo-Lin Hou, Jun Yin, Miriayi Alimujiang, Xue-Ying Yu, Li-Gen Ai, Yu-Qian Bao, Fang Liu, Wei-Ping Jia
Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes...
November 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29104783/expression-levels-of-the-uridine-cytidine-kinase-like-1-protein-as-a-novel-prognostic-factor-for-hepatitis-c-virus-associated-hepatocellular-carcinomas
#19
A Buivydiene, V Liakina, J Valantinas, J Norkuniene, E Mockiene, S Jokubauskiene, R Smaliukiene, L Jancoriene, L Kovalevska, E Kashuba
The expression levels of the two novel oncoproteins uridine-cytidine kinase like-1 (UCKL-1) and mitochondrial ribosomal protein S18-2 (MRPS18-2) were assessed in samples of hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) using immunohistochemistry. Tissue microarray (TMA) paraffin blocks were prepared from 42 HCC tumor samples with the corresponding peri-tumor tissues and from 11 tissues of a liver with HCV-induced cirrhosis. We found that the UCKL-1 signal in the liver tissues of the peri-tumor zone in the HCC samples was stronger than that in cirrhosis (50 ± 49...
July 2017: Acta Naturae
https://www.readbyqxmd.com/read/29104729/mitochondria-targeted-antioxidants-skq1-and-mitotempo-failed-to-exert-a-long-term-beneficial-effect-in-murine-polymicrobial-sepsis
#20
Pia Rademann, Adelheid Weidinger, Susanne Drechsler, Andras Meszaros, Johannes Zipperle, Mohammad Jafarmadar, Sergiu Dumitrescu, Ara Hacobian, Luisa Ungelenk, Franziska Röstel, Jozsef Kaszaki, Andrea Szabo, Vladimir P Skulachev, Michael Bauer, Soheyl Bahrami, Sebastian Weis, Andrey V Kozlov, Marcin F Osuchowski
Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO) improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice (n = 90) underwent cecal ligation and puncture (CLP) and received SkQ1 (5 nmol/kg), MitoTEMPO (50 nmol/kg), or vehicle 5 times post-CLP. Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints...
2017: Oxidative Medicine and Cellular Longevity
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