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Article ; Online: Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus-Host Interactions.

Kakkanas, Athanassios / Karamichali, Eirini / Koufogeorgou, Efthymia Ioanna / Kotsakis, Stathis D / Georgopoulou, Urania / Foka, Pelagia

Biomolecules

2022 Volume 12, Issue 8

Abstract: The emerging SARS-CoV and SARS-CoV-2 belong to the family of "common cold" RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes ... ...

Abstract	The emerging SARS-CoV and SARS-CoV-2 belong to the family of "common cold" RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes for the accessory protein ORF3a, with unclear functions, possibly related to viral virulence and pathogenesis. The tyrosine-based YXXΦ motif (Φ: bulky hydrophobic residue-L/I/M/V/F) was originally discovered to mediate clathrin-dependent endocytosis of membrane-spanning proteins. Many viruses employ the YXXΦ motif to achieve efficient receptor-guided internalisation in host cells, maintain the structural integrity of their capsids and enhance viral replication. Importantly, this motif has been recently identified on the ORF3a proteins of SARS-CoV and SARS-CoV-2. Given that the ORF3a aa sequence is not fully conserved between the two SARS viruses, we aimed to map in silico structural differences and putative sequence-driven alterations of regulatory elements within and adjacently to the YXXΦ motifs that could predict variations in ORF3a functions. Using robust bioinformatics tools, we investigated the presence of relevant post-translational modifications and the YXXΦ motif involvement in protein-protein interactions. Our study suggests that the predicted YXXΦ-related features may confer specific-yet to be discovered-functions to ORF3a proteins, significant to the new virus and related to enhanced propagation, host immune regulation and virulence.
MeSH term(s)	COVID-19 ; Host Microbial Interactions ; Humans ; Peptides ; Severe acute respiratory syndrome-related coronavirus/genetics ; SARS-CoV-2
Chemical Substances	Peptides
Language	English
Publishing date	2022-07-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12081052
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Epigenetic Controller Lysine-Specific Demethylase 1 (LSD1) Regulates the Outcome of Hepatitis C Viral Infection.

Papadopoulou, Georgia / Petroulia, Stavroula / Karamichali, Eirini / Dimitriadis, Alexios / Marousis, Dimitrios / Ioannidou, Elisavet / Papazafiri, Panagiota / Koskinas, John / Foka, Pelagia / Georgopoulou, Urania

Cells

2023 Volume 12, Issue 21

Abstract: Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. The host epigenetic changes induced by HCV lead to metabolic dysfunction and malignant transformation. Lysine- ...

Abstract	Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. The host epigenetic changes induced by HCV lead to metabolic dysfunction and malignant transformation. Lysine-specific demethylase 1 (LSD1) is an epigenetic controller of critical cellular functions that are essential for HCV propagation. We investigated the putative role of LSD1 in the establishment of HCV infection using genetic engineering and pharmacological inhibition to alter endogenous LSD1 levels. We demonstrated for the first time that HCV replication was inhibited in LSD1-overexpressing cells, while specific HCV proteins differentially fine-tuned endogenous LSD1 expression levels. Electroporation of the full-length HCV genome and subgenomic replicons in LSD1 overexpression enhanced translation and partially restored HCV replication, suggesting that HCV might be inhibited by LSD1 during the early steps of infection. Conversely, the inhibition of LSD1, followed by HCV infection in vitro, increased viral replication. LSD1 was shown to participate in an intriguing antiviral mechanism, where it activates endolysosomal interferon-induced transmembrane protein 3 (IFITM3) via demethylation, leading endocytosed HCV virions to degradation. Our study proposes that HCV-mediated LSD1 oscillations over countless viral life cycles throughout chronic HCV infection may promote epigenetic changes related to HCV-induced hepatocarcinogenesis.
MeSH term(s)	Humans ; Hepacivirus/physiology ; Lysine/metabolism ; Hepatitis C/genetics ; Histone Demethylases/metabolism ; Epigenesis, Genetic ; Membrane Proteins/metabolism ; RNA-Binding Proteins/metabolism
Chemical Substances	Lysine (K3Z4F929H6) ; Histone Demethylases (EC 1.14.11.-) ; IFITM3 protein, human ; Membrane Proteins ; RNA-Binding Proteins
Language	English
Publishing date	2023-11-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12212568
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Article ; Online: Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment.

Valiakou, Vaia / Eliadis, Petros / Karamichali, Eirini / Tsitsilonis, Ourania / Koskinas, John / Georgopoulou, Urania / Foka, Pelagia

International journal of molecular sciences

2021 Volume 22, Issue 15

Abstract: Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does ... ...

Abstract	Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does not always protect against hepatocellular carcinoma (HCC). Angiopoietin-like protein-3 (ANGPTL-3) and angiopoietin-like protein-4 (ANGPTL-4) regulate the clearance of plasma lipids by inhibiting cellular lipase activity and possess emerging roles in tumourigenesis. We used ELISA and RT-qPCR to investigate ANGPTL-3 and ANGPTL-4 expression in HCV patients with characterised fibrosis throughout the natural history of hepatitis C and in long-term HCV infection in vitro, before and after DAA treatment. ANGPTL-3 was decreased in patients with advanced fibrosis compared to other disease stages, while ANGPTL-4 was progressively increased from acute infection to cirrhosis and HCC, peaking at the advanced fibrosis stage. Only ANGPTL-3 mRNA was down-regulated during early infection in vitro, although both ANGPTLs were increased later. DAA treatment did not alter ANGPTL-3 levels in advanced fibrosis/cirrhosis and in HCV infection in vitro, in contrast to ANGPTL-4. The association between ANGPTLs and fibrosis in HCV infection was underlined by an inverse correlation between the levels of ANGPTLs and serum transforming growth factor- β (TGF-β). Collectively, we demonstrate the pivotal role of advanced fibrosis in defining the expression fate of ANGPTLs in HCV infection and after treatment and propose a role for ANGPTL-3 as a contributor to post-treatment deregulation of lipid metabolism that could predispose certain individuals to HCC development.
MeSH term(s)	Angiopoietin-like 4 Protein/biosynthesis ; Angiopoietin-like Proteins/biosynthesis ; Antiviral Agents/administration & dosage ; Cell Line, Tumor ; Female ; Gene Expression Regulation/drug effects ; Hepacivirus/metabolism ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/metabolism ; Humans ; Liver Cirrhosis/drug therapy ; Liver Cirrhosis/metabolism ; Male
Chemical Substances	ANGPTL3 protein, human ; ANGPTL4 protein, human ; Angiopoietin-like 4 Protein ; Angiopoietin-like Proteins ; Antiviral Agents
Language	English
Publishing date	2021-07-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22157961
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Article ; Online: Hepatitis Viruses Control Host Immune Responses by Modifying the Exosomal Biogenesis Pathway and Cargo.

Karamichali, Eirini / Foka, Pelagia / Papadopoulou, Georgia / Loukaki-Gkountara, Domniki / Andresaki, Konstantina / Koskinas, Ioannis / Georgopoulou, Urania

International journal of molecular sciences

2022 Volume 23, Issue 18

Abstract: The development of smart immune evasion mechanisms is crucial for the establishment of acute and chronic viral hepatitis. Hepatitis is a major health problem worldwide arising from different causes, such as pathogens, metabolic disorders, and xenotoxins, ...

Abstract	The development of smart immune evasion mechanisms is crucial for the establishment of acute and chronic viral hepatitis. Hepatitis is a major health problem worldwide arising from different causes, such as pathogens, metabolic disorders, and xenotoxins, with the five hepatitis viruses A, B, C, D, and E (HAV, HBV, HCV, HDV, and HEV) representing the majority of the cases. Most of the hepatitis viruses are considered enveloped. Recently, it was reported that the non-enveloped HAV and HEV are, in reality, quasi-enveloped viruses exploiting exosomal-like biogenesis mechanisms for budding. Regardless, all hepatitis viruses use exosomes to egress, regulate, and eventually escape from the host immune system, revealing another key function of exosomes apart from their recognised role in intercellular communication. This review will discuss how the hepatitis viruses exploit exosome biogenesis and transport capacity to establish successful infection and spread. Then, we will outline the contribution of exosomes in viral persistence and liver disease progression.
MeSH term(s)	Cell Communication ; Hepatitis Viruses ; Hepatitis, Chronic ; Hepatitis, Viral, Human ; Humans ; Immunity
Language	English
Publishing date	2022-09-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231810862
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Article ; Online: Photodynamic Inactivation of Bovine Coronavirus with the Photosensitizer Toluidine Blue O.

Zaharieva, Maya Margaritova / Foka, Pelagia / Karamichali, Eirini / Kroumov, Alexander Dimitrov / Philipov, Stanislav / Ilieva, Yana / Kim, Tanya Chan / Podlesniy, Petar / Manasiev, Yordan / Kussovski, Vesselin / Georgopoulou, Urania / Najdenski, Hristo Miladinov

Viruses

2023 Volume 16, Issue 1

Abstract: Coronaviruses (CoVs) belong to the group of enveloped positive-sense single-strand RNA viruses and are causative agents of respiratory, gastro-intestinal, and central nervous systems diseases in many host species, i.e., birds, mammals, and humans. Beta- ... ...

Abstract	Coronaviruses (CoVs) belong to the group of enveloped positive-sense single-strand RNA viruses and are causative agents of respiratory, gastro-intestinal, and central nervous systems diseases in many host species, i.e., birds, mammals, and humans. Beta-CoVs revealed a great potential to cross the barrier between species by causing three epidemics/pandemics among humans in the 21st century. Considering the urgent need for powerful antiviral agents for decontamination, prevention, and treatment of BCoV infections, we turned our attention to the possibility of photodynamic inactivation with photosensitizers in combination with light irradiation. In the present study, we evaluated, for the first time, the antiviral activity of toluidine blue O (TBO) against Beta-coronavirus 1 (BCoV) in comparison to methylene blue (MB). First, we determined the in vitro cytotoxicity of MB and TBO on the Madin-Darby bovine kidney (MDBK) cell line with ISO10993-5/Annex C. Thereafter, BCoV was propagated in MDBK cells, and the virus titer was measured with digital droplet PCR, TCID
MeSH term(s)	Humans ; Cattle ; Animals ; Coronavirus, Bovine ; Photosensitizing Agents/pharmacology ; Tolonium Chloride/pharmacology ; Coronavirus ; Coronavirus Infections ; Methylene Blue ; Pandemics ; Antiviral Agents/pharmacology ; Mammals
Chemical Substances	Photosensitizing Agents ; Tolonium Chloride (15XUH0X66N) ; Methylene Blue (T42P99266K) ; Antiviral Agents
Language	English
Publishing date	2023-12-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010048
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Article ; Online: HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis.

Foka, Pelagia / Dimitriadis, Alexios / Karamichali, Eirini / Kochlios, Emmanouil / Eliadis, Petros / Valiakou, Vaia / Koskinas, John / Mamalaki, Avgi / Georgopoulou, Urania

Cells

2021 Volume 10, Issue 9

Abstract: Iron is crucial to the regulation of the host innate immune system and the outcome of many infections. Hepatitis C virus (HCV), one of the major viral human pathogens that depends on iron to complete its life cycle, is highly skilled in evading the ... ...

Abstract	Iron is crucial to the regulation of the host innate immune system and the outcome of many infections. Hepatitis C virus (HCV), one of the major viral human pathogens that depends on iron to complete its life cycle, is highly skilled in evading the immune system. This study presents the construction and validation of a physiologically relevant triple-cell co-culture model that was used to investigate the input of iron in HCV infection and the interplay between HCV, iron, and determinants of host innate immunity. We recorded the expression patterns of key proteins of iron homeostasis involved in iron import, export and storage and examined their relation to the iron regulatory hormone hepcidin in hepatocytes, enterocytes and macrophages in the presence and absence of HCV. We then assessed the transcriptional profiles of pro-inflammatory cytokines Interleukin-6 (IL-6) and interleukin-15 (IL-15) and anti-inflammatory interleukin-10 (IL-10) under normal or iron-depleted conditions and determined how these were affected by infection. Our data suggest the presence of a link between iron homeostasis and innate immunity unfolding among liver, intestine, and macrophages, which could participate in the deregulation of innate immune responses observed in early HCV infection. Coupled with iron-assisted enhanced viral propagation, such a mechanism may be important for the establishment of viral persistence and the ensuing chronic liver disease.
MeSH term(s)	Coculture Techniques ; Cytokines/metabolism ; Enterocytes/immunology ; Enterocytes/metabolism ; Enterocytes/pathology ; Enterocytes/virology ; Hepacivirus/immunology ; Hepacivirus/metabolism ; Hepatitis C/immunology ; Hepatitis C/metabolism ; Hepatitis C/pathology ; Hepatitis C/virology ; Hepatocytes/immunology ; Hepatocytes/metabolism ; Hepatocytes/pathology ; Hepatocytes/virology ; Homeostasis ; Humans ; Immunity, Innate ; Iron/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/pathology ; Macrophages/virology
Chemical Substances	Cytokines ; Iron (E1UOL152H7)
Language	English
Publishing date	2021-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10092251
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Article ; Online: Post-COVID-19 Parkinsonism and Parkinson's Disease Pathogenesis: The Exosomal Cargo Hypothesis.

Mysiris, Dimitrios S / Vavougios, George D / Karamichali, Eirini / Papoutsopoulou, Stamatia / Stavrou, Vasileios T / Papayianni, Eirini / Boutlas, Stylianos / Mavridis, Theodoros / Foka, Pelagia / Zarogiannis, Sotirios G / Gourgoulianis, Konstantinos / Xiromerisiou, Georgia

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, ... ...

Abstract	Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.
MeSH term(s)	COVID-19/complications ; Cell Communication ; Humans ; Neurodegenerative Diseases ; Parkinson Disease/metabolism ; Parkinsonian Disorders/etiology ; Parkinsonian Disorders/pathology ; RNA, Viral ; SARS-CoV-2 ; alpha-Synuclein/metabolism
Chemical Substances	RNA, Viral ; alpha-Synuclein
Language	English
Publishing date	2022-08-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23179739
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Article ; Online: The Hepatitis C virus NS5A and core proteins exert antagonistic effects on HAMP gene expression: the hidden interplay with the MTF-1/MRE pathway.

Dimitriadis, Alexios / Foka, Pelagia / Kyratzopoulou, Eleni / Karamichali, Eirini / Petroulia, Stavroula / Tsitoura, Panagiota / Kakkanas, Athanasios / Eliadis, Petros / Georgopoulou, Urania / Mamalaki, Avgi

FEBS open bio

2020 Volume 11, Issue 1, Page(s) 237–250

Abstract: Hepcidin, a 25-amino acid peptide encoded by the HAMP gene and produced mainly by hepatocytes and macrophages, is a mediator of innate immunity and the central iron-regulatory hormone. Circulating hepcidin controls iron efflux by inducing degradation of ... ...

Abstract	Hepcidin, a 25-amino acid peptide encoded by the HAMP gene and produced mainly by hepatocytes and macrophages, is a mediator of innate immunity and the central iron-regulatory hormone. Circulating hepcidin controls iron efflux by inducing degradation of the cellular iron exporter ferroportin. HCV infection is associated with hepatic iron overload and elevated serum iron, which correlate with poor antiviral responses. The HCV nonstructural NS5A protein is known to function in multiple aspects of the HCV life cycle, probably exerting its activity in concert with cellular factor(s). In this study, we attempted to delineate the effect of HCV NS5A on HAMP gene expression. We observed that transient transfection of hepatoma cell lines with HCV NS5A resulted in down-regulation of HAMP promoter activity. A similar effect was evident after transduction of Huh7 cells with a recombinant baculovirus vector expressing NS5A protein. We proceeded to construct an NS5A-expressing stable cell line, which also exhibited down-regulation of HAMP gene promoter activity and significant reduction of HAMP mRNA and hepcidin protein levels. Concurrent expression of HCV core protein, a well-characterized hepcidin inducer, revealed antagonism between those two proteins for hepcidin regulation. In attempting to identify the pathways involved in NS5A-driven reduction of hepcidin levels, we ruled out any NS5A-induced alterations in the expression of the well-known hepcidin inducers SMAD4 and STAT3. Further analysis linked the abundance of intracellular zinc ions and the deregulation of the MTF-1/MRE/hepcidin axis with the observed phenomenon. This effect could be associated with distinct phases in HCV life cycle.
MeSH term(s)	Cell Line, Tumor ; DNA-Binding Proteins/metabolism ; Hepacivirus/immunology ; Hepacivirus/metabolism ; Hepatitis C/genetics ; Hepatitis C/immunology ; Hepatitis C/virology ; Hepatocytes/metabolism ; Hepatocytes/virology ; Hepcidins/genetics ; Host Microbial Interactions/genetics ; Host Microbial Interactions/immunology ; Humans ; Immunity, Innate/genetics ; Iron/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Promoter Regions, Genetic/genetics ; Transcription Factors/metabolism ; Viral Core Proteins/metabolism ; Viral Nonstructural Proteins/isolation & purification ; Transcription Factor MTF-1
Chemical Substances	DNA-Binding Proteins ; HAMP protein, human ; Hepcidins ; Transcription Factors ; Viral Core Proteins ; Viral Nonstructural Proteins ; nucleocapsid protein, Hepatitis C virus ; Iron (E1UOL152H7) ; NS-5 protein, hepatitis C virus (EC 2.7.7.48)
Language	English
Publishing date	2020-12-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13048
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Article ; Online: Hepcidin and the iron enigma in HCV infection.

Georgopoulou, Urania / Dimitriadis, Alexios / Foka, Pelagia / Karamichali, Eirini / Mamalaki, Avgi

Virulence

2014 Volume 5, Issue 4, Page(s) 465–476

Abstract: An estimated 30-40% of patients with chronic hepatitis C have elevated serum iron, transferrin saturation, and ferritin levels. Clinical data suggest that iron is a co-morbidity factor for disease progression following HCV infection. Iron is essential ... ...

Abstract	An estimated 30-40% of patients with chronic hepatitis C have elevated serum iron, transferrin saturation, and ferritin levels. Clinical data suggest that iron is a co-morbidity factor for disease progression following HCV infection. Iron is essential for a number of fundamental metabolic processes in cells and organisms. Mammalian iron homeostasis is tightly regulated and this is maintained through the coordinated action of sensory and regulatory networks that modulate the expression of iron-related proteins at the transcriptional and/or posttranscriptional levels. Disturbances of iron homeostasis have been implicated in infectious disease pathogenesis. Viruses, similarly to other pathogens, can escape recognition by the immune system, but they need iron from their host to grow and spread. Hepcidin is a 25-aa peptide, present in human serum and urine and represents the key peptide hormone, which modulates iron homeostasis in the body. It is synthesized predominantly by hepatocytes and its mature form is released in circulation. In this review, we discuss recent advances in the exciting crosstalk of molecular mechanisms and cell signaling pathways by which iron and hepcidin production influences HCV-induced liver disease.
MeSH term(s)	Animals ; Hepacivirus/physiology ; Hepatitis C, Chronic/metabolism ; Hepatitis C, Chronic/virology ; Hepcidins/metabolism ; Humans ; Iron/metabolism ; Liver/metabolism ; Liver/virology
Chemical Substances	Hepcidins ; Iron (E1UOL152H7)
Language	English
Publishing date	2014-03-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2657572-3
ISSN	2150-5608 ; 2150-5594
ISSN (online)	2150-5608
ISSN	2150-5594
DOI	10.4161/viru.28508
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Article: Molecular characterization of the Xenopus CCAAT-enhancer binding protein beta gene promoter.

Foka, P / Kousteni, S / Ramji, D P

Biochemical and biophysical research communications

2001 Volume 285, Issue 2, Page(s) 430–436

Abstract: Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family play key roles in the regulation of genes implicated in the control of growth, differentiation, metabolism, and inflammation. The recent limited studies on the promoter ... ...

Abstract	Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family play key roles in the regulation of genes implicated in the control of growth, differentiation, metabolism, and inflammation. The recent limited studies on the promoter regions of C/EBP genes, particularly C/EBPalpha, have indicated the potential existence of species-specific regulatory mechanisms. It is therefore essential that the promoter regions of different C/EBP genes from a wide range of species are investigated in detail. As an important step toward this goal, we report here the characterization of the Xenopus laevis C/EBPbeta gene promoter. Sequence analysis showed that the 1.6-kb promoter region contained putative binding sites for several transcription factors that have previously been implicated in the regulation of the C/EBPs, including C/EBP, CREB, Myb, STAT, and USF. The -288/+91 promoter region was capable of directing high levels of expression in the hepatoma Hep3B cell line. In addition, this minimal promoter could be autoregulated by both C/EBPalpha and C/EBPbeta and activated by lipopolysaccharide, interleukin-6 and CREB. These results therefore demonstrate that several aspects of C/EBPbeta regulation in mammals have been highly conserved in amphibians. However, a comparison of C/EBPbeta gene promoters characterized to date does indicate the existence of species-specific differences in autoregulation.
MeSH term(s)	Animals ; Base Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Protein-beta/genetics ; CCAAT-Enhancer-Binding Protein-beta/metabolism ; Carcinoma, Hepatocellular ; Conserved Sequence ; Cyclic AMP Response Element-Binding Protein/metabolism ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Interleukin-6/pharmacology ; Lipopolysaccharides/pharmacology ; Liver Neoplasms ; Molecular Sequence Data ; Promoter Regions, Genetic ; Rats ; Recombinant Proteins/metabolism ; Sequence Analysis, DNA ; TATA Box ; Transcription Factors/metabolism ; Transfection ; Tumor Cells, Cultured ; Xenopus laevis/genetics
Chemical Substances	CCAAT-Enhancer-Binding Protein-beta ; Cyclic AMP Response Element-Binding Protein ; DNA-Binding Proteins ; Interleukin-6 ; Lipopolysaccharides ; Recombinant Proteins ; Transcription Factors
Language	English
Publishing date	2001-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1006/bbrc.2001.5203
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