Potential Molecular Mechanisms of Viral Liver Carcinogenesis

1996 ◽  
pp. 183-196
Author(s):  
M. S. De Mitri ◽  
P. Baccarini ◽  
C. Bonazzi ◽  
P. Paterlini ◽  
E. Pisi
Keyword(s):  
Molecular Mechanisms ◽  
Liver Carcinogenesis

scholarly journals Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zhanpeng Wang ◽  
Zhuonan Li ◽  
Yanshuo Ye ◽  
Lijuan Xie ◽  
Wei Li
Keyword(s):  
Oxidative Stress ◽  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
The Body ◽  
Liver Carcinogenesis ◽  
Cancer Etiology ◽  
Nonalcoholic Fatty Liver ◽  
The Impact ◽  
The Relationship

Accumulating evidence has indicated that oxidative stress (OS) is associated with the development of hepatocellular carcinoma (HCC). However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD). The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC.

scholarly journals Molecular Mechanisms of Liver Carcinogenesis in the Mdr2-Knockout Mice

2007 ◽  
Vol 5 (11) ◽  
pp. 1159-1170 ◽  
Author(s):  
Mark Katzenellenbogen ◽  
Lina Mizrahi ◽  
Orit Pappo ◽  
Naama Klopstock ◽  
Devorah Olam ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Molecular Mechanisms ◽  
Liver Carcinogenesis

scholarly journals Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis

2019 ◽  
Vol 216 (4) ◽  
pp. 950-965 ◽  
Author(s):  
Yoshiharu Muto ◽  
Toshiro Moroishi ◽  
Kazuya Ichihara ◽  
Masaaki Nishiyama ◽  
Hideyuki Shimizu ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Genetically Engineered ◽  
Liver Carcinogenesis ◽  
Cellular Iron ◽  
Hepatic Iron Overload ◽  
Genetically Engineered Mouse Model ◽  
Compensatory Proliferation ◽  
Cellular Iron Homeostasis

Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload elicited by FBXL5 ablation gave rise to oxidative stress, tissue damage, inflammation, and compensatory proliferation of hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting outcome of FBXL5 deficiency in the liver was also found to be effective in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis promoted by iron overload. In addition, dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human HCC, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.

Prunus Armeniaca L. Seed Extract and Its Amygdalin Containing Fraction Induced Mitochondrial-Mediated Apoptosis and Autophagy in Liver Carcinogenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Samar Hosny ◽  
Heba Sahyon ◽  
Magdy Youssef ◽  
Amr Negm
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Inflammatory Marker ◽  
Flow Cytometric Analysis ◽  
Beclin 1 ◽  
Nuclear Antigen ◽  
Therapeutic Effects ◽  
Liver Carcinogenesis ◽  
In Vitro Investigation

Background: Despite significant advances in therapeutic interventions, liver cancer is the leading cause of cancer mortality in the world. Potential phytochemicals have shown to be promising agents against many life-threatening diseases because of their low toxicity and potential effectiveness. Objective: The current study aims to an in vitro investigation of the anticancer activity of Apricot Extract (AE) and Amygdalin Containing Fraction (ACF), additionally studying their therapeutic effects in DMBA-induced liver carcinogenesis mice model to highlight their related biochemical and molecular mechanisms. Methods and Results: Amygdalin was isolated from the seeds of P. armeniaca L. Male mice received AE or ACF, DMBA, DMBA+AE, DMBA+ACF, and vehicles. The oxidative stress and antioxidant markers, cell proliferation by flow cytometric analysis of Proliferating Cell Nuclear Antigen (PCNA) expression, angiogenesis marker (VEGF), inflammatory marker (TNF-α), apoptotic, anti-apoptotic and autophagy genes expression (caspase-3, Bcl-2, and Beclin-1) were investigated.AE and ACF were found to stimulate the apoptotic process by up-regulating caspase-3 expression and down-regulating Bcl-2 expression. They also reduce VEGF and PCNA levels and increasing the antioxidant defense system. Moreover, AE and ACF treatments also inhibit HepG2 and EAC cell proliferation and up-regulate Beclin-1 expression. Conclusion: This study provides evidence that, in DMBA-induced hepatocarcinogenesis, the key proteins involved in the proliferation, angiogenesis, autophagy, and apoptosis are feasible molecular targets for hepatothrapeutic potential using AE and ACF.

scholarly journals Molecular Mechanisms of Fibrosis-Associated Promotion of Liver Carcinogenesis

2013 ◽  
Vol 132 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Takeki Uehara ◽  
Garrett R. Ainslie ◽  
Kristi Kutanzi ◽  
Igor P. Pogribny ◽  
Levan Muskhelishvili ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Liver Carcinogenesis

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

Dissection of the molecular mechanisms of protein targeting to the peroxisome using immunofluorescence and immunocryoelectron microscopies

1990 ◽  
Vol 48 (3) ◽  
pp. 44-45
Author(s):  
G-A. Keller ◽  
S. J. Gould ◽  
S. Subramani ◽  
S. Krisans
Keyword(s):  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Protein Targeting ◽  
Firefly Luciferase ◽  
Peroxisomal Enzyme ◽  
Transfected Cells ◽  
Peroxisomal Targeting ◽  
Targeting Signal ◽  
Series Of Experiments ◽  
Peroxisomal Targeting Signal

Subcellular compartments within eukaryotic cells must each be supplied with unique sets of proteins that must be directed to, and translocated across one or more membranes of the target organelles. This transport is mediated by cis- acting targeting signals present within the imported proteins. The following is a chronological account of a series of experiments designed and carried out in an effort to understand how proteins are targeted to the peroxisomal compartment.-We demonstrated by immunocryoelectron microscopy that the enzyme luciferase is a peroxisomal enzyme in the firefly lantern. -We expressed the cDNA encoding firefly luciferase in mammalian cells and demonstrated by immunofluorescence that the enzyme was transported into the peroxisomes of the transfected cells. -Using deletions, linker insertions, and gene fusion to identify regions of luciferase involved in its transport to the peroxisomes, we demonstrated that luciferase contains a peroxisomal targeting signal (PTS) within its COOH-terminal twelve amino acid.

High resolution mapping of nucleic acid containing complexes in vitro and in situ

1996 ◽  
Vol 54 ◽  
pp. 48-49
Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel
Keyword(s):  
Nucleic Acid ◽  
High Resolution ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Heavy Atom ◽  
Regulation Of Transcription ◽  
High Exposure ◽  
Resolution Mapping ◽  
Tata Sequence

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Sign in / Sign up

Export Citation Format

Share Document