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https://www.readbyqxmd.com/read/29018408/levels-of-hepatic-activating-transcription-factor-6-and-caspase-3-are-downregulated-in-mice-after-excessive-training
#1
Ana P Pinto, Alisson L da Rocha, Luciana da C Oliveira, Gustavo P Morais, Larissa G de Vicente, Dennys E Cintra, José R Pauli, Leandro P Moura, Eduardo R Ropelle, Adelino S R da Silva
Recently, we demonstrated that different running overtraining (OT) protocols with the same external load, but performed downhill (OTR/down), uphill (OTR/up), and without inclination (OTR), led to hepatic fat accumulation. As the disruption of endoplasmic reticulum (ER) homeostasis is linked to animal models of fatty liver disease, we investigated the effects of these OT models on the proteins related to ER stress (i.e., BiP, inositol-requiring enzyme 1, protein kinase RNA-like endoplasmic reticulum kinase, eIF2alpha, ATF6beta, and glucose-regulated protein 94) and apoptosis (C/EBP-homologous protein, Caspase-3, 4, and 12, Bax, and tumor necrosis factor receptor-associated factor 2) in livers of C57BL/6 mice...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#2
Eunüs S Ali, Grigori Y Rychkov, Greg J Barritt
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca(2+) in the lumen of the ER. In steatotic hepatocytes, store-operated Ca(2+) entry (SOCE) is substantially inhibited...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28797256/selenoprotein-s-a-therapeutic-target-for-diabetes-and-macroangiopathy
#3
REVIEW
Shan-Shan Yu, Jian-Ling Du
Inflammatory response, oxidative stress, and endoplasmic reticulum (ER) stress are important pathophysiological bases of the occurrence and development of diabetes mellitus (DM) and macroangiopathy complications. Selenoprotein S (SELENOS) is involved in the regulation of these mechanisms; therefore, its association with DM and macroangiopathy has gradually received attention from scholars worldwide. SELENOS has different biological functions in different tissues and organs: it exerts antioxidant protection and has anti-ER stress effects in the pancreas and blood vessels, while it promotes the occurrence and development of insulin resistance in the liver, adipose tissue, and skeletal muscle...
August 10, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28768569/tissue-cell-stress-response-to-obesity-and-its-interaction-with-late-gestation-diet
#4
Vivek Saroha, Neele S Dellschaft, Duane H Keisler, David S Gardner, Helen Budge, Sylvain P Sebert, Michael E Symonds
Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic health in the offspring. In the present study we used an animal (sheep) model of maternal dietary manipulation in late pregnancy, combined with exposure of the offspring to a low-activity, obesogenic environment after weaning, to characterise the effects on glucose homeostasis. Dizygotic twin-pregnant sheep were either fed to 60% of requirements (nutrient restriction (R)) or fed ad libitum (~140% of requirements (A)) from 110 days gestation until term (~147 days)...
August 3, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28752441/pathophysiology-of-alpha-1-antitrypsin-deficiency-liver-disease
#5
Jeffrey H Teckman, Keith S Blomenkamp
Classical alpha-1 antitrypsin (a1AT) deficiency is an autosomal recessive disease associated with an increased risk of liver disease in adults and children, and with lung disease in adults (Teckman and Jain, Curr Gastroenterol Rep 16(1):367, 2014). The vast majority of the liver disease is associated with homozygosity for the Z mutant allele, the so-called PIZZ. These homozygous individuals synthesize large quantities of a1AT mutant Z protein in the liver, but the mutant protein folds improperly during biogenesis and approximately 85% of the molecules are retained within the hepatocytes rather than appropriately secreted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28694862/primary-hepatic-marginal-zone-lymphoma-in-a-patient-with-chronic-hepatitis-c
#6
George S Gherlan, Razvan Stoia, Mihaly Enyedi, Camelia Dobrea, Petre I Calistru
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is a low-grade malignant lymphoma that appears frequently in the stomach, but other sites can also be involved: the intestinal tract, lungs, head, neck, skin, thyroid, breasts and liver. Recently, epidemiological evidences support the idea that there is an association between hepatitis C and B-cell non-Hodgkin lymphomas (that include MALT as a subtype). Primary non-Hodgkin lymphomas confi ned only to the liver are very rare (only 0...
September 2016: Mædica
https://www.readbyqxmd.com/read/28551485/spontaneous-submental-hematoma-a-pseudo-ludwig-s-phenomenon-in-101-year-old-patient-case-report-and-literature-review
#7
Uthman Alamoudi, Yasser Alsallumi, Matthew H Rigby, S Mark Taylor, Jonathan R B Trites, Robert D Hart
OBJECTIVE: Submental hematoma or pseudo-Ludwig's phenomenon, is a rare entity seen in anticoagulated patients and can precipitate upper airway obstruction. Our objective is to present a rare case of spontaneous submental hematoma due to poorly controlled hypertension in elderly patient and to perform a literature review. CASE REPORT: 101-year-old female presented to emergency room with sudden painful swelling in the floor of mouth and slurred speech. Not on anticoagulation and no history of trauma or known allergies...
2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28323103/cr-vi-induces-cytotoxicity-in-vitro-through-activation-of-ros-mediated-endoplasmic-reticulum-stress-and-mitochondrial-dysfunction-via-the-pi3k-akt-signaling-pathway
#8
Yujing Zhang, Fang Xiao, Xinmin Liu, Kaihua Liu, Xiaoxin Zhou, Caigao Zhong
The occupational and environmental toxicant hexavalent chromium [Cr(VI)] can cause severe damage to the liver; however, the exact mechanisms associated with its toxicity have not been thoroughly demonstrated. In the present study, the underlying mechanisms of Cr(VI)-induced hepatotoxicity were investigated. Our results showed that Cr(VI) inhibited the growth and proliferation of L-02 hepatocytes. Further study revealed that Cr(VI) significantly induced S-phase cell cycle arrest and apoptosis accompanying with the overproduction of reactive oxygen species (ROS)...
March 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28052021/serum-hepatitis-b-core-antibody-titer-use-in-screening-for-significant-fibrosis-in-treatment-na%C3%A3-ve-patients-with-chronic-hepatitis-b
#9
Min-Ran Li, Huan-Wei Zheng, Jian-Hua Lu, Shun-Mao Ma, Li-Hong Ye, Zhi-Quan Liu, Hai-Cong Zhang, Yun-Yan Liu, Ying Lv, Yan Huang, Er-Hei Dai, Dian-Xing Sun
BACKGROUND: Previous studies have revealed that hepatitis B core antibody (anti-HBc) levels vary throughout the different phases of treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of treatment response in both interferon-α and nucleoside analogue therapies. However, few data have been published regarding the relationship between quantitative anti-HBc (qAnti-HBc) levels and liver fibrosis in patients with CHB. RESULTS: A total of 489 HBeAg-positive (HBeAg (+)) and 135 HBeAg-negative (HBeAg (-)) patients were recruited...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/27909053/endoplasmic-reticulum-stress-and-ca2-depletion-differentially-modulate-the-sterol-regulatory-protein-pcsk9-to-control-lipid-metabolism
#10
Paul Lebeau, Ali Al-Hashimi, Sudesh Sood, Šárka Lhoták, Pei Yu, Gabriel Gyulay, Guillaume Paré, S R Wayne Chen, Bernardo Trigatti, Annik Prat, Nabil G Seidah, Richard C Austin
Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER-localized transcription factor that directly up-regulates sterol regulatory genes, including PCSK9 Given that PCSK9 contributes to atherosclerosis by targeting low density lipoprotein (LDL) receptor (LDLR) degradation, this study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27683551/prevention-of-atherosclerosis-by-bioactive-palmitoleate-through-suppression-of-organelle-stress-and-inflammasome-activation
#11
Ismail Çimen, Begüm Kocatürk, Seda Koyuncu, Özlem Tufanlı, Umut I Onat, Asli D Yıldırım, Onur Apaydın, Şeyma Demirsoy, Zaliha G Aykut, Uyen T Nguyen, Steven M Watkins, Gökhan S Hotamışlıgil, Ebru Erbay
De novo lipogenesis (DNL), the conversion of glucose and other substrates to lipids, is often associated with ectopic lipid accumulation, metabolic stress, and insulin resistance, especially in the liver. However, organ-specific DNL can also generate distinct lipids with beneficial metabolic bioactivity, prompting a great interest in their use for the treatment of metabolic diseases. Palmitoleate (PAO), one such bioactive lipid, regulates lipid metabolism in liver and improves glucose utilization in skeletal muscle when it is generated de novo from the obese adipose tissue...
September 28, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27601439/the-endoplasmic-reticulum-remains-functionally-connected-by-vesicular-transport-after-its-fragmentation-in-cells-expressing-z-%C3%AE-1-antitrypsin
#12
Jennifer A Dickens, Adriana Ordóñez, Joseph E Chambers, Alison J Beckett, Vruti Patel, Elke Malzer, Caia S Dominicus, Jayson Bradley, Andrew A Peden, Ian A Prior, David A Lomas, Stefan J Marciniak
α1-Antitrypsin is a serine protease inhibitor produced in the liver that is responsible for the regulation of pulmonary inflammation. The commonest pathogenic gene mutation yields Z-α1-antitrypsin, which has a propensity to self-associate forming polymers that become trapped in inclusions of endoplasmic reticulum (ER). It is unclear whether these inclusions are connected to the main ER network in Z-α1-antitrypsin-expressing cells. Using live cell imaging, we found that despite inclusions containing an immobile matrix of polymeric α1-antitrypsin, small ER resident proteins can diffuse freely within them...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27022162/endoplasmic-reticulum-stress-up-regulates-nedd4-2-to-induce-autophagy
#13
Hao Wang, Ruo-Qiong Sun, Daria Camera, Xiao-Yi Zeng, Eunjung Jo, Stanley M H Chan, Terence P Herbert, Juan C Molero, Ji-Ming Ye
The accumulation of unfolded proteins within the endoplasmic reticulum (ER) causes ER stress and activation of unfolded protein response (UPR). This response can trigger ER-associated degradation and autophagy, which clear unfolded proteins and restore protein homeostasis. Recently, it has become clear that ubiquitination plays an important role in the regulation of autophagy. In the present study, we investigated how the E3 ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4-2 (Nedd4-2) interacts with ER stress and autophagy...
July 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/26804600/hepatocellular-carcinoma-and-estrogen-receptors-polymorphisms-and-isoforms-relations-and-implications
#14
V D Baldissera, A F Alves, S Almeida, M Porawski, M Giovenardi
Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and its incidence continues to increase worldwide. HCC is a disease with multifactorial causes and genetic variability has been discussed as a risk factor for its development. Liver is a hormone-sensitive organ and therefore is influenced by gonadal hormones, such as estrogen. Estrogen is known to participate in various biological functions, but its role in development of HCC, on the other hand, is controversial and presents evidence suggesting a role as both a carcinogen and protective effect in liver...
January 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/26762307/clinically-advanced-and-metastatic-pure-mucinous-carcinoma-of-the-breast-a-comprehensive-genomic-profiling-study
#15
Jeffrey S Ross, Laurie M Gay, Sahar Nozad, Kai Wang, Siraj M Ali, Ann Boguniewicz, Depinder Khaira, Adrienne Johnson, Julia A Elvin, Jo-Anne Vergilio, James Suh, Vincent A Miller, Philip J Stephens
PURPOSE: Pure mucinous breast carcinoma (pmucBC) is a distinctive variant of breast cancer (BC) featuring an excellent overall prognosis. However, on rare occasions, pmucBC pursues an aggressive clinical course. We queried whether comprehensive genomic profiling (CGP) would uncover clinically relevant genomic alterations (CRGA) that could lead to targeted therapy treatment for patients with an advanced and metastatic form of pmucBC. METHODS: From a series of 51,238 total cancer samples, which included 5605 cases of clinically advanced BC and 22 cases of stage IV pmucBC, DNA was extracted from 40 microns of FFPE sections...
January 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/26567840/possible-involvement-of-multidrug-resistant-hepatitis-b-virus-sw172-truncation-variant-in-the-er-stress-signaling-pathway-during-hepatocarcinogenesis
#16
Jiajia Zheng, Suzhen Jiang, Fengmin Lu
We investigated the biological effect of hepatitis B virus (HBV) rtA181T/sW172* point mutation on HBsAg secretion and the potential mechanisms involved in hepatocarcinogenesis. Full-length HBV wild type (wt) and HBV rtA181T/sW172* expression plasmids were transfected into HepG2 cell lines or were injected into C57BL/6 mice. The extracellular and intracellular expression levels of HBsAg and HBeAg proteins, in mouse serum and liver tissues were detected by ELISA. The localization of the truncated protein was characterized in vitro...
July 22, 2016: Japanese Journal of Infectious Diseases
https://www.readbyqxmd.com/read/26078563/induction-of-endoplasmic-reticulum-derived-oxidative-stress-by-an-occult-infection-related-s-surface-antigen-variant
#17
In-Kyung Lee, Seoung-Ae Lee, Hong Kim, You-Sub Won, Bum-Joon Kim
AIM: To investigate the mechanism of endoplasmic reticulum (ER) stress induction by an occult infection related hepatitis B virus S surface antigen (HBsAg) variant. METHODS: We used an HBsAg variant with lower secretion capacity, which was a KD variant from a Korean subject who was occultly infected with the genotype C. We compared the expression profiles of ER stress-related proteins between HuH-7 cells transfected with HBsAg plasmids of a wild-type and a KD variant using Western blot...
June 14, 2015: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/25937070/o-glcnacylation-of-eif2%C3%AE-regulates-the-phospho-eif2%C3%AE-mediated-er-stress-response
#18
Insook Jang, Han Byeol Kim, Hojoong Seo, Jin Young Kim, Hyeonjin Choi, Jong Shin Yoo, Jae-woo Kim, Jin Won Cho
O-GlcNAcylation is highly involved in cellular stress responses including the endoplasmic reticulum (ER) stress response. For example, glucosamine-induced flux through the hexosamine biosynthetic pathway can promote ER stress and ER stress inducers can change the total cellular level of O-GlcNAcylation. However, it is largely unknown which component(s) of the unfolded protein response (UPR) is directly regulated by O-GlcNAcylation. In this study, eukaryotic translation initiation factor 2α (eIF2α), a major branch of the UPR, was O-GlcNAcylated at Ser 219, Thr 239, and Thr 241...
August 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25743375/hepatitis-c-virus-structural-proteins-can-exacerbate-or-ameliorate-acetaminophen-induced-liver-injury-in-mice
#19
Anup Ramachandran, Margitta Lebofsky, Hui-Min Yan, Steven A Weinman, Hartmut Jaeschke
Chronic hepatitis C virus (HCV) infection predisposes patients to develop liver failure after acetaminophen (APAP) overdose. Mechanisms involved in this were explored using transgenic mice expressing the HCV structural proteins core, E1 and E2. Treatment of C57BL/6J mice with 200 mg/kg body weight APAP resulted in significant liver injury at 6 h as indicated by elevated ALT levels, focal centrilobular necrosis and nuclear DNA fragmentation. HCV transgenic mice showed a variable response, with approximately half the animals showing exacerbation of all parameters of liver injury, while the other half was protected...
May 2015: Archives of Toxicology
https://www.readbyqxmd.com/read/25475897/luminal-breast-cancer-metastases-and-tumor-arousal-from-dormancy-are-promoted-by-direct-actions-of-estradiol-and-progesterone-on-the-malignant-cells
#20
Ndiya Ogba, Nicole G Manning, Brian S Bliesner, S Kelly Ambler, James M Haughian, Mauricio P Pinto, Paul Jedlicka, Kristiina Joensuu, Päivi Heikkilä, Kathryn B Horwitz
INTRODUCTION: Luminal, estrogen receptor-positive (ER(+)) breast cancers can metastasize but lie dormant for years before recurrences prove lethal. Understanding the roles of estrogen (E) or progestin (P) in development of luminal metastases or in arousal from dormancy is hindered by few preclinical models. We have developed such models. METHODS: Immunocompromised, ovariectomized (ovx'd) mice were intracardiac-injected with luminal or basal human breast cancer cells...
2014: Breast Cancer Research: BCR
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