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https://www.readbyqxmd.com/read/28321271/parkin-in-cancer-mitophagy-related-unrelated-tasks
#1
EDITORIAL
Nabil Eid, Yoichi Kondo
Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondria via a process termed mitophagy, Parkin-mediated mitophagy may be a tumor-suppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28252653/endogenous-ampk-acts-as-a-detrimental-factor-in-fulminant-hepatitis-via-potentiating-jnk-dependent-hepatocyte-apoptosis
#2
Kai Hu, Xianqiong Gong, Qing Ai, Ling Lin, Jie Dai, Lu Cai, Rong Jiang, Pu Ge, Li Zhang
The energy sensor AMP-activated protein kinase (AMPK) is crucial for energy homeostasis. Recent studies have revealed that AMPK is involved in various energy-intensive pathological processes such as inflammation and apoptosis. The physiological functions of hepatic AMPK have been well studied, but the pathological significance of AMPK in liver disorders remains largely unknown. In the present study, the phosphorylation status and the roles of AMPK were investigated in mice with lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced fulminant hepatitis...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28212554/afb1-hepatocarcinogenesis-is-via-lipid-peroxidation-that-inhibits-dna-repair-sensitizes-mutation-susceptibility-and-induces-aldehyde-dna-adducts-at-p53-mutational-hotspot-codon-249
#3
Mao-Wen Weng, Hyun-Wook Lee, Bongkun Choi, Hsiang-Tsui Wang, Yu Hu, Manju Mehta, Dhimant Desai, Shantu Amin, Yi Zheng, Moon-Shong Tang
Aflatoxin B1 (AFB1) contamination in the food chain is a major cause of hepatocellular carcinoma (HCC). More than 60% of AFB1 related HCC carry p53 codon 249 mutations but the causal mechanism remains unclear. We found that 1) AFB1 induces two types of DNA adducts in human hepatocytes, AFB1-8,9-epoxide-deoxyguanosine (AFB1-E-dG) induced by AFB1-E and cyclic α-methyl-γ-hydroxy-1,N2-propano-dG (meth-OH-PdG) induced by lipid peroxidation generated acetaldehyde (Acet) and crotonaldehyde (Cro); 2) the level of meth-OH-PdG is >30 fold higher than the level of AFB1-E-dG; 3) AFB1, Acet, and Cro, but not AFB1-E, preferentially induce DNA damage at codon 249; 4) methylation at -CpG- sites enhances meth-OH-PdG formation at codon 249; and 5) repair of meth-OH-PdG at codon 249 is poor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28166970/effects-of-intrauterine-growth-restriction-during-late-pregnancy-on-the-cell-apoptosis-and-related-gene-expression-in-ovine-fetal-liver
#4
Yingchun Liu, Chi Ma, Hui Li, Lingyao Li, Feng Gao, Changjin Ao
This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver. Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.18 MJ ME kg BW(-0.75) d(-1), n = 6), Restricted Group 2 (RG2, 0.33 MJ ME kg BW(-0.75) d(-1), n = 6) and a Control Group (CG, ad libitum, 0.67 MJ ME kg BW (-0.75) d (-1), n = 6). Fetuses were recovered at slaughter on d 140...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28130345/the-piddosome-activates-p53-in-response-to-supernumerary-centrosomes
#5
Luca L Fava, Fabian Schuler, Valentina Sladky, Manuel D Haschka, Claudia Soratroi, Lisa Eiterer, Egon Demetz, Guenter Weiss, Stephan Geley, Erich A Nigg, Andreas Villunger
Centrosomes, the main microtubule-organizing centers in animal cells, are replicated exactly once during the cell division cycle to form the poles of the mitotic spindle. Supernumerary centrosomes can lead to aberrant cell division and have been causally linked to chromosomal instability and cancer. Here, we report that an increase in the number of mature centrosomes, generated by disrupting cytokinesis or forcing centrosome overduplication, triggers the activation of the PIDDosome multiprotein complex, leading to Caspase-2-mediated MDM2 cleavage, p53 stabilization, and p21-dependent cell cycle arrest...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28121078/research-highlights
#6
(no author information available yet)
In this issue, we highlight work from Cecchinato et al. revealing a technique for restoring chemotaxis in HIV-infected Th17 cells, a study by Wei et al. showing that Yersinia pestis YopM is an E3 ligase that can regulate host inflammasomes, a paper by Prokesch et al. reporting that p53 regulates metabolic adaptation to starvation in normal hepatocytes and work from Singh et al. that shows that Salmonella acquires nutrients from host cells by hijacking chaperone-mediated autophagy.
January 2017: FEBS Journal
https://www.readbyqxmd.com/read/28119452/microrna-375-is-induced-in-cisplatin-nephrotoxicity-to-repress-hepatocyte-nuclear-factor-1-beta
#7
Jielu Hao, Qiang Lou, Qingqing Wei, Shuqin Mei, Lin Li, Qing-Sheng Mi, Changlin Mei, Zheng Dong
Nephrotoxicity is a major adverse effect of cisplatin-mediated chemotherapy in cancer patients. The pathogenesis of cisplatin-induced nephrotoxicity remains largely unclear, making it difficult to design effective renoprotective approaches. Here, we have examined the role of microRNAs (miRNAs) in cisplatin-induced nephrotoxicity. We show that cisplatin nephrotoxicity was not affected by overall depletion of both beneficial and detrimental miRNAs from kidney proximal tubular cells in mice in which the miRNA-generating enzyme Dicer had been conditionally knocked out...
January 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28088184/anti-hepatitis-b-virus-hbv-response-of-imiquimod-based-toll-like-receptor-7-ligand-in-hbv-positive-human-hepatocelluar-carcinoma-cell-line
#8
Dipanwita Das, Isha Sengupta, Neelakshi Sarkar, Ananya Pal, Debraj Saha, Manikankana Bandopadhyay, Chandrima Das, Jimmy Narayan, Shivaram Prasad Singh, Sekhar Chakrabarti, Runu Chakravarty
BACKGROUND: Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. METHODS: The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837...
January 14, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28075444/the-role-of-lncrna-malat1-in-the-regulation-of-hepatocyte-proliferation-during-liver-regeneration
#9
Cuicui Li, Lei Chang, Zhiquan Chen, Zhongzhong Liu, Yanfeng Wang, Qifa Ye
Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) not only regulates tumorigenesis in hepatocellular carcinoma, but also controls cell cycle progression in hematopoietic cells. The present study was designed to investigate the biological role of lncRNA MALAT1 in liver regeneration. We carried out a series of assays during liver regeneration following 2/3 partial hepatectomy in mice...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28059455/acetoacetate-induces-hepatocytes-apoptosis-by-the-ros-mediated-mapks-pathway-in-ketotic-cows
#10
Xiliang Du, Zhen Shi, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Zhe Wang, Xiaobing Li, Guowen Liu, Xinwei Li
Dairy cows with ketosis are characterized by oxidative stress, hepatic damage and hyperketonemia. Acetoacetate (AA) is the main component of ketone bodies in ketotic cows, and is associated with the above pathological process. However, the potential mechanism was not illuminated. Therefore, the aim of this study was to investigate the mechanism of AA-induced hepatic oxidative damage in ketotic cows. Compared with healthy cows, ketotic cows exhibited severe oxidative stress and hepatic damage. Moreover, the extent of hepatic damage and oxidative stress had a positive relationship with the AA levels...
January 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27956228/genome-wide-crispr-screen-identifies-regulators-of-mitogen-activated-protein-kinase-as-suppressors-of-liver-tumors-in-mice
#11
Chun-Qing Song, Yingxiang Li, Haiwei Mou, Jill Moore, Angela Park, Yotsawat Pomyen, Soren Hough, Zachary Kennedy, Andrew Fischer, Hao Yin, Daniel G Anderson, Darryl Conte, Lars Zender, Xin Wei Wang, Snorri Thorgeirsson, Zhiping Weng, Wen Xue
BACKGROUND & AIMS: It has been a challenge to identify liver tumor suppressors or oncogenes due to the genetic heterogeneity of these tumors. We performed a genome-wide screen to identify suppressors of liver tumor formation in mice, using CRISPR-mediated genome editing. METHODS: We performed a genome-wide CRISPR/Cas9-based knockout screen of P53-null mouse embryonic liver progenitor cells that overexpressed MYC. We infected p53(-/-);Myc;Cas9 hepatocytes with the mGeCKOa lentiviral library of 67,000 single-guide RNAs (sgRNAs), targeting 20,611 mouse genes, and transplanted the transduced cells subcutaneously into nude mice...
December 10, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27902328/hepatitis-c-virus-core-activates-proteasomal-activator-28%C3%AE-expression-via-upregulation-of-p53-levels-to-control-virus-propagation
#12
Juri Kwak, Indira Tiwari, Kyung Lib Jang
The proteasomal activator 28γ (PA28γ), frequently overexpressed in hepatocellular carcinoma, is believed to play several important roles in hepatitis C virus (HCV) replication and viral pathogenesis. However, the underlying mechanism for PA28γ overexpression in hepatocellular carcinoma and its role during HCV replication are still unclear. In the present study, we found that HCV core derived from either ectopic expression or HCV infection upregulates PA28γ levels in p53-positive human hepatocytes. For this effect, HCV core sequentially activated ataxia telangiectasia mutated and checkpoint kinase 2 via phosphorylation at Ser-1981 and Thr-68 residues, respectively, resulting in stabilization of p53 via phosphorylation at Ser-15 and Ser-20 residues and subsequent transcriptional activation of PA28γ expression...
January 2017: Journal of General Virology
https://www.readbyqxmd.com/read/27853236/regulation-of-sirt1-nrf2-tnf-%C3%AE-signaling-pathway-by-luteolin-is-critical-to-attenuate-acute-mercuric-chloride-exposure-induced-hepatotoxicity
#13
Daqian Yang, Xiao Tan, Zhanjun Lv, Biying Liu, Ruiqi Baiyun, Jingjing Lu, Zhigang Zhang
Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832471/expression-pattern-of-bccip-in-hepatocellular-carcinoma-is-correlated-with-poor-prognosis-and-enhanced-cell-proliferation
#14
Zhipeng Lin, Baoying Hu, Wenkai Ni, Xiaofei Mao, Huiling Zhou, Jiale Lv, Bihui Yin, Zhongyi Shen, Miaomiao Wu, Wensen Ding, Mingbing Xiao, Runzhou Ni
BCCIP was originally identified as a BRCA2- and CDKN1A- (Cip1/waf1/p21) interacting protein, also known as BCCIP. It has been reported to express in various types of cancers, including colorectal cancer (CRC), astrocytic brain tumors, and glioblastomas. However, the relationship between BCCIP expression and clinicopathological features of hepatocellular carcinoma (HCC) remains to be determined. Herein, we demonstrated that BCCIP was downregulated in clinical HCC tissues; its level was inversely correlated with multiple clinicopathological factors, such as tumor grade, tumor size, and Ki67 expression...
November 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27824900/sirt6-depletion-suppresses-tumor-growth-by-promoting-cellular-senescence-induced-by-dna-damage-in-hcc
#15
Namgyu Lee, Hye Guk Ryu, Jung-Hee Kwon, Dae-Kyum Kim, Sae Rom Kim, Hee Jung Wang, Kyong-Tai Kim, Kwan Yong Choi
The role of Sirtuin 6 (SIRT6) as a tumor suppressor or oncogene in liver cancer remains controversial. Thus, we identified the specific role of SIRT6 in the progression of hepatocellular carcinoma (HCC). SIRT6 expression was significantly higher in HCC cell lines and HCC tissues from 138 patients than in an immortalized hepatocyte cell line, THLE-2 and non-tumor tissues, respectively. SIRT6 knockdown by shRNA suppressed the growth of HCC cells and inhibited HCC tumor growth in vivo. In addition, SIRT6 silencing significantly prevented the growth of HCC cell lines by inducing cellular senescence in the p16/Rb- and p53/p21-pathway independent manners...
2016: PloS One
https://www.readbyqxmd.com/read/27811061/liver-p53-is-stabilized-upon-starvation-and-required-for-amino-acid-catabolism-and-gluconeogenesis
#16
Andreas Prokesch, Franziska A Graef, Tobias Madl, Jennifer Kahlhofer, Steffi Heidenreich, Anne Schumann, Elisabeth Moyschewitz, Petra Pristoynik, Astrid Blaschitz, Miriam Knauer, Matthias Muenzner, Juliane G Bogner-Strauss, Gottfried Dohr, Tim J Schulz, Michael Schupp
The ability to adapt cellular metabolism to nutrient availability is critical for survival. The liver plays a central role in the adaptation to starvation by switching from glucose-consuming processes and lipid synthesis to providing energy substrates like glucose to the organism. Here we report a previously unrecognized role of the tumor suppressor p53 in the physiologic adaptation to food withdrawal. We found that starvation robustly increases p53 protein in mouse liver. This induction was posttranscriptional and mediated by a hepatocyte-autonomous and AMP-activated protein kinase-dependent mechanism...
November 3, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27791012/notch3-drives-development-and-progression-of-cholangiocarcinoma
#17
Rachel V Guest, Luke Boulter, Benjamin J Dwyer, Timothy J Kendall, Tak-Yung Man, Sarah E Minnis-Lyons, Wei-Yu Lu, Andrew J Robson, Sofia Ferreira Gonzalez, Alexander Raven, Davina Wojtacha, Jennifer P Morton, Mina Komuta, Tania Roskams, Stephen J Wigmore, Owen J Sansom, Stuart J Forbes
The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27770462/il-6-trans-signaling-is-essential-for-the-development-of-hepatocellular-carcinoma-in-mice
#18
Juri Bergmann, Miryam Müller, Niklas Baumann, Manuel Reichert, Carola Heneweer, Julia Bolik, Karsten Lücke, Sabine Gruber, Antonella Carambia, Susanne Boretius, Ivo Leuschner, Thomas Becker, Björn Rabe, Johannes Herkel, F Thomas Wunderlich, Hans-Willi Mittrücker, Stefan Rose-John, Dirk Schmidt-Arras
Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine, interleukin-6 (IL-6), is a critical mediator of HCC development. It can signal through two distinct pathways: the IL-6 classic and the IL-6 trans-signaling pathway. Whereas IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet...
January 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27764939/nrf2-knockdown-disrupts-the-protective-effect-of-curcumin-on-alcohol-induced-hepatocyte-necroptosis
#19
Chunfeng Lu, Wenxuan Xu, Feng Zhang, Jiangjuan Shao, Shizhong Zheng
It has emerged that hepatocyte necroptosis plays a critical role in chronic alcoholic liver disease (ALD). Our previous study has identified that the beneficial therapeutic effect of curcumin on alcohol-caused liver injury might be attributed to activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), whereas the role of curcumin in regulating necroptosis and the underlying mechanism remain to be determined. We first found that chronic alcohol consumption triggered obvious hepatocyte necroptosis, leading to increased expression of receptor-interacting protein 1, receptor-interacting protein 3, high-mobility group box 1, and phosphorylated mixed lineage kinase domain-like in murine livers...
December 5, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27756472/%C3%AE-hydroxybutyrate-induces-bovine-hepatocyte-apoptosis-via-an-ros-p38-signaling-pathway
#20
Yuxiang Song, Na Li, Jingmin Gu, Shoupeng Fu, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Xiaobing Li, Zhe Wang, Xinwei Li, Guowen Liu
β-Hydroxybutyrate (BHB) is an important indicator for metabolic disorders in dairy cows, such as ketosis and fatty liver. Dairy cows with ketosis display oxidative stress that may be associated with high levels of BHB. The purpose of this study was to demonstrate a correlation between the high levels of BHB and oxidative stress in dairy cows with ketosis, and to investigate the molecular mechanisms underlying oxidative damage in bovine hepatocytes. The results showed that dairy cows with ketosis exhibited oxidative stress and liver damage, which was significantly correlated with plasma BHB...
November 2016: Journal of Dairy Science
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