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https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#1
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28747430/ferredoxin-reductase-is-critical-for-p53-dependent-tumor-suppression-via-iron-regulatory-protein-2
#2
Yanhong Zhang, Yingjuan Qian, Jin Zhang, Wensheng Yan, Yong-Sam Jung, Mingyi Chen, Eric Huang, Kent Lloyd, Yuyou Duan, Jian Wang, Gang Liu, Xinbin Chen
Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to iron overload in developing embryos. Interestingly, mice heterozygous in Fdxr had a short life span and were prone to spontaneous tumors and liver abnormalities, including steatosis, hepatitis, and hepatocellular carcinoma...
July 26, 2017: Genes & Development
https://www.readbyqxmd.com/read/28746875/kmt5a-controls-hepatic-metabolic-pathways-by-facilitating-rna-pol-ii-release-from-promoter-proximal-regions
#3
Kostas C Nikolaou, Panagiotis Moulos, Vangelis Harokopos, George Chalepakis, Iannis Talianidis
H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. Here, we show that, in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28744811/evidence-of-vanillin-binding-to-camkiv-explains-the-anti-cancer-mechanism-in-human-hepatic-carcinoma-and-neuroblastoma-cells
#4
Huma Naz, Mohd Tarique, Parvez Khan, Suaib Luqman, Shahzaib Ahamad, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr kinase family, and is associated with different types of cancer and neurodegenerative diseases. Vanillin is a natural compound, a primary component of the extract of the vanilla bean which possesses varieties of pharmacological features including anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor. Here, we have investigated the binding mechanism and affinity of vanillin to the CAMKIV which is being considered as a potential drug target for cancer and neurodegenerative diseases...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28744018/cxcl10-is-produced-in-hepatitis-a-virus-infected-cells-in-an-irf3-dependent-but-ifn-independent-manner
#5
Pil Soo Sung, Seon-Hui Hong, Jeewon Lee, Su-Hyung Park, Seung Kew Yoon, Woo Jin Chung, Eui-Cheol Shin
Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by severe liver injury in adult patients, and the liver injury is associated with the production of chemokines. Herein, we investigated the mechanism of how HAV infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10, CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2 cells. In particular, CXCL10 was produced in HAV-infected cells, not in neighboring uninfected cells...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733671/short-chain-fatty-acids-and-inulin-but-not-guar-gum-prevent-diet-induced-obesity-and-insulin-resistance-through-differential-mechanisms-in-mice
#6
Karolin Weitkunat, Christin Stuhlmann, Anna Postel, Sandra Rumberger, Maria Fankhänel, Anni Woting, Klaus Jürgen Petzke, Sabrina Gohlke, Tim J Schulz, Michael Blaut, Susanne Klaus, Sara Schumann
The role of dietary fibre and short-chain fatty acids (SCFA) in obesity development is controversially discussed. Here, we investigated how various types of dietary fibre and different SCFA ratios affect metabolic syndrome-related disorders. Male mice (B6) were fed high-fat diets supplemented with dietary fibres (either cellulose, inulin or guar gum) or different Ac:Pr ratios (high acetate (HAc) or propionate (HPr)) for 30 weeks. Body-fat gain and insulin resistance were greatly reduced by inulin, but not by guar gum, and completely prevented by SCFA supplementation...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28727777/8-oxoguanine-dna-glycosylase-ogg1-deficiency-elicits-coordinated-changes-in-lipid-and-mitochondrial-metabolism-in-muscle
#7
Vladimir Vartanian, Jana Tumova, Pawel Dobrzyn, Agnieszka Dobrzyn, Yusaku Nakabeppu, R Stephen Lloyd, Harini Sampath
Oxidative stress resulting from endogenous and exogenous sources causes damage to cellular components, including genomic and mitochondrial DNA. Oxidative DNA damage is primarily repaired via the base excision repair pathway that is initiated by DNA glycosylases. 8-oxoguanine DNA glycosylase (OGG1) recognizes and cleaves oxidized and ring-fragmented purines, including 8-oxoguanine, the most commonly formed oxidative DNA lesion. Mice lacking the OGG1 gene product are prone to multiple features of the metabolic syndrome, including high-fat diet-induced obesity, hepatic steatosis, and insulin resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28726269/previous-physical-exercise-alters-hepatic-profile-of-oxidative-inflammatory-status-and-limits-the-secondary-brain-damage-induced-by-severe-tbi-in-rats
#8
Mauro Robson Torres de Castro, Ana Paula de Oliveira Ferreira, Guilherme Lago Busanello, Luís Roberto Hart da Silva, Mauro Eduardo Porto da Silveira Junior, Fernando Fiorin, Gabriela Arrifano, Maria Elena Crespo López, Rômulo Pillon Barcelos, María J Cuevas, Guilherme Bresciani, Javier González-Gallego, Michele Rechia Fighera, Luiz Fernando Freire Royes
Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. In this sense, we decided to investigate whether peripheral oxidative/inflammatory response contributes to the neuronal dysfunction after TBI as well as prophylactic role of exercise training. Animals were submitted to fluid percussion injury (FPI) after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha (LXR-α), ATP-binding cassette transporter (ABCA1), and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 expression per se in liver...
July 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28725667/data-on-lipocalin-2-and-phosphatidylinositol-3-kinase-signaling-in-a-methionine-and-choline-deficient-model-of-non-alcoholic-steatohepatitis
#9
Anastasia Asimakopoulou, Erawan Borkham-Kamphorst, Eddy Van de Leur, Ralf Weiskirchen
The data presented in this brief report support the research article "Altered mitochondrial and peroxisomal integrity in lipocalin-2-deficient mice with hepatic steatosis" [1, doi: 10.1016/j.bbadis.2017.04.006]. We tested whether the absence of Lipocalin-2 (LCN2) could dysregulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K-PKB) pathway and hepatic homeostasis in Non-Alcoholic-Steatohepatitis (NASH). The article highlights the role of LCN2 in hepatic homeostasis.
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28724855/decreased-fatty-acid-%C3%AE-oxidation-is-the-main-cause-of-fatty-liver-induced-by-polyunsaturated-fatty-acid-deficiency-in-mice
#10
Takero Nakajima, Yang Yang, Yu Lu, Yuji Kamijo, Yosuke Yamada, Kozo Nakamura, Masahiro Koyama, Shohei Yamaguchi, Eiko Sugiyama, Naoki Tanaka, Toshifumi Aoyama
Insufficient intake of polyunsaturated fatty acids (PUFA) causes fatty liver. The mechanism responsible is primarily related to increased lipogenesis and decreased FA degradation based on rodent studies. However, these studies were limited by the fact that the typical PUFA-deficient diets contained insufficient amounts of long-chain FA, the PUFA-containing diets were primarily composed of n-3 PUFA-enriched oil, and the intake of PUFA was excessive compared with the physiological requirement. To address these issues, mice were fed a PUFA-deficient diet containing long-chain FA at a standard fed level and then were orally fed a n-3/n-6-balanced PUFA-containing oil [PUFA (+)] or a PUFA-deficient oil [PUFA (-)] at physiological relevant levels (0...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28724791/mitochondrial-dna-enriched-microparticles-promote-acute-on-chronic-alcoholic-neutrophilia-and-hepatotoxicity
#11
Yan Cai, Ming-Jiang Xu, Erik H Koritzinsky, Zhou Zhou, Wei Wang, Haixia Cao, Peter St Yuen, Ruth A Ross, Robert A Star, Suthat Liangpunsakul, Bin Gao
Over the last several years, one of the major advances in the field of alcoholic liver disease research was the discovery that binge alcohol consumption induced neutrophilia and hepatic neutrophil infiltration in chronically ethanol-fed mice and human subjects with excessive alcohol use (EAU); however, the underlying mechanisms remain obscure. Here, we demonstrated that chronic EAU patients with a history of recent excessive drinking (EAU + RD) had higher serum levels of mitochondrial DNA (mtDNA)-enriched microparticles (MPs) than EAU without recent drinking (EAU - RD) and healthy controls, which correlated positively with circulating neutrophils...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28723568/loss-of-hepatic-mitochondrial-long-chain-fatty-acid-oxidation-confers-resistance-to-diet-induced-obesity-and-glucose-intolerance
#12
Jieun Lee, Joseph Choi, Ebru S Selen Alpergin, Liang Zhao, Thomas Hartung, Susanna Scafidi, Ryan C Riddle, Michael J Wolfgang
The liver has a large capacity for mitochondrial fatty acid β-oxidation, which is critical for systemic metabolic adaptations such as gluconeogenesis and ketogenesis. To understand the role of hepatic fatty acid oxidation in response to a chronic high-fat diet (HFD), we generated mice with a liver-specific deficiency of mitochondrial long-chain fatty acid β-oxidation (Cpt2(L-/-) mice). Paradoxically, Cpt2(L-/-) mice were resistant to HFD-induced obesity and glucose intolerance with an absence of liver damage, although they exhibited serum dyslipidemia, hepatic oxidative stress, and systemic carnitine deficiency...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#13
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28717105/ephedrine-induced-mitophagy-via-oxidative-stress-in-human-hepatic-stellate-cells
#14
Ah Young Lee, Yoonjeong Jang, Seong-Ho Hong, Seung-Hee Chang, Sungjin Park, Sanghwa Kim, Kyung-Sun Kang, Ji-Eun Kim, Myung-Haing Cho
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28713991/pien-tze-huang-gan-bao-attenuates-carbon-tetrachloride%C3%A2-induced-hepatocyte-apoptosis-in-rats-associated-with-suppression-of-p53-activation-and-oxidative-stress
#15
Jinyan Zhao, Yuchen Zhang, Yun Wan, Haixia Hu, Zhenfeng Hong
Pien Tze Huang Gan Bao (PZH‑GB), a traditional Chinese medicine, has been used for thousands of years as a protective remedy effective against liver injury induced by excessive alcohol and smoking. The present study aimed to evaluate the protective effects and potential mechanisms of PZH‑GB against carbon tetrachloride (CCl4)‑induced hepatic injury. Rats were pre‑treated with silymarin (50 mg/kg) or different doses of PZH‑GB (150, 300 or 600 mg/kg) orally administered for 7 days. At the end of treatment, the rats were intraperitoneally injected with CCl4, or control rats received a corn oil injection...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712316/disturbed-bovine-mitochondrial-lipid-metabolism-a-review
#16
J H van der Kolk, J J Gross, V Gerber, R M Bruckmaier
In mammals, excess energy is stored primarily as triglycerides, which are mobilized when energy demands arise and cannot be covered by feed intake. This review mainly focuses on the role of long chain fatty acids in disturbed energy metabolism of the bovine species. Long chain fatty acids regulate energy metabolism as ligands of peroxisome proliferator-activated receptors. β-Oxidation is the process by which fatty acid molecules are broken down in the mitochondria or peroxisomes to generate acetyl-CoA. Carnitine acts as a carrier of fatty acyl groups as long-chain acyl-CoA derivatives do not penetrate the mitochondrial inner membrane...
July 17, 2017: Veterinary Quarterly
https://www.readbyqxmd.com/read/28711683/anti-obesogenic-effects-of-wy14643-ppar-alpha-agonist-hepatic-mitochondrial-enhancement-and-suppressed-lipogenic-pathway-in-diet-induced-obese-mice
#17
Flavia Maria Silva Veiga, Francielle Graus-Nunes, Tamiris Lima Rachid, Aline Barcellos Barreto, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
Non-alcoholic fatty liver disease (NAFLD) presents with growing prevalence worldwide, though its pharmacological treatment remains to be established. This study aimed to evaluate the effects of a PPAR-alpha agonist on liver tissue structure, ultrastructure, and metabolism, focusing on gene and protein expression of de novo lipogenesis and gluconeogenesis pathways, in diet-induced obese mice. Male C57BL/6 mice (three months old) received a control diet (C, 10% of lipids, n = 10) or a high-fat diet (HFD, 50% of lipids, n = 10) for ten weeks...
July 12, 2017: Biochimie
https://www.readbyqxmd.com/read/28711594/hepatic-mitochondrial-bioenergetics-in-aged-c57bl-6-mice-exhibit-delayed-recovery-from-severe-burn-injury
#18
Christopher Auger, Thibacg Sivayoganathan, Abdikarim Abdullahi, Alexandra Parousis, Marc G Jeschke
Severe burn injuries initiate a cascade of downstream events, culminating in multiple organ dysfunction, sepsis, and even death. The elderly are in particular vulnerable to such outcomes, due primarily to a scarcity of knowledge on trauma progression at the biomolecular level in this population. Mitochondria, the cellular powerhouses, have been increasingly scrutinized recently for their contribution to trauma outcomes. We hypothesized that elderly have a worse outcome compared to adult patients due to failed recovery of hepatic mitochondria...
July 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28704337/alleviation-of-ischemia-reperfusion-injury-in-liver-steatosis-by-augmenter-of-liver-regeneration-alr-is-attributed-to-antioxidation-and-preservation-of-mitochondria
#19
Junhua Weng, Wen Li, Xiaowei Jia, Wei An
BACKGROUND: Fatty liver is 1 of the major impediments to liver surgery and liver transplantation because steatotic hepatocytes are more susceptible to ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated. METHODS: In vivo, liver steatosis of mice was induced by feeding a methionine-choline deficient diet for 2 weeks. Three days prior to hepatic partial warm IRI, mice were transfected with the ALR-containing adenovirus...
July 13, 2017: Transplantation
https://www.readbyqxmd.com/read/28701883/20s-protopanaxadiol-an-aglycosylated-ginsenoside-metabolite-induces-hepatic-stellate-cell-apoptosis-through-liver-kinase-b1-amp-activated-protein-kinase-activation
#20
Sang Mi Park, Eun Hye Jung, Jae Kwang Kim, Kyung Hwan Jegal, Chung A Park, Il Je Cho, Sang Chan Kim
BACKGROUND: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. METHODS: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides...
July 2017: Journal of Ginseng Research
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