scholarly journals EVA1A Plays an Important Role by Regulating Autophagy in Physiological and Pathological Processes

2021 ◽  
Vol 22 (12) ◽  
pp. 6181
Author(s):  
Shizhen Zhao ◽  
Honggang Wang
Keyword(s):  
Cardiac Remodeling ◽  
Theoretical Basis ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Sequence Similarity ◽  
Disease Development ◽  
Cell Functions ◽  
Embryonic Neurogenesis ◽  
B Virus

Eva-1 homolog A (EVA1A) is regarded as TMEM166 (transmembrane protein 166) or FAM176A (family with sequence similarity 176) and a lysosome and endoplasmic reticulum-associated protein involved in regulating autophagy and apoptosis. EVA1A regulates embryonic neurogenesis, cardiac remodeling, islet alpha-cell functions, acute liver failure, and hepatitis B virus replication. However, the related mechanisms are not fully clear. Autophagy is a process in which cells transfer pathogens, abnormal proteins and organelles to lysosomes for degradation. It plays an important role in various physiological and pathological processes, including cancer, aging, neurodegeneration, infection, heart disease, development, cell differentiation and nutritional starvation. Recently, there are many studies on the important role of EVA1A in many physiological and pathological processes by regulating autophagy. However, the related molecular mechanisms need further study. Therefore, we summarize the above-mentioned researches about the role of EVA1A in physiological and pathological processes through regulating autophagy in order to provide theoretical basis for future researches.

scholarly journals The roles and mechanisms of hypoxia in liver fibrosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyao Cai ◽  
Min Hu ◽  
Zhiyang Chen ◽  
Zeng Ling
Keyword(s):  
Quality Of Life ◽  
Liver Fibrosis ◽  
Theoretical Basis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Clinical Intervention ◽  
Chronic Liver Injury ◽  
Key Factor

AbstractLiver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.

scholarly journals Role of Transmembrane Domains of Hepatitis B Virus Small Surface Proteins in Subviral-Particle Biogenesis

2012 ◽  
Vol 87 (3) ◽  
pp. 1491-1496 ◽  
Author(s):  
Vera D. Siegler ◽  
Volker Bruss
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transmembrane Protein ◽  
Transmembrane Domains ◽  
Surface Proteins ◽  
Wild Type ◽  
Small Surface ◽  
Huh7 Cells ◽  
B Virus

ABSTRACTThe hepatitis B virus (HBV) surface proteins not only are incorporated into the virion envelope but in addition form subviral particles (SVP) consisting solely of surface proteins and lipids. Heterologous expression of the small HBV envelope protein S produces secreted spherical SVP 20 nm in diameter, with approximately 100 S molecules per particle. The pathway leading from the initial S translation product as a multispanning transmembrane protein to the final SVP is largely unknown. To investigate the role of the four transmembrane domains (TM) of S in this process, we introduced mutations in these regions and characterized their effects on SVP formation in transfected Huh7 cells. We found that the insertion of one amino acid in the center of the α-helix of TM1 or the exchange of TM1 with a heterologous TM blocked SVP release and SVP formation by coexpressed wild-type S chains in a transdominant negative fashion. Surprisingly, this effect was partially neutralized when the mutations were expressed in the background of the HBV surface protein M, suggesting that mutations in TM1 could partially be complemented by the pre-S2 domain. The exchange of TM2 with heterologous TMs that form α-helices of the same lengths was also incompatible with SVP formation. However, these mutants no longer blocked SVP formation by coexpressed wild-type S. We conclude that TM2 is essential for the stable assembly of S chains by establishing intramembrane interactions.

scholarly journals ARPEGGIO: Automated Reproducible Polyploid EpiGenetic GuIdance workflOw

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stefan Milosavljevic ◽  
Tony Kuo ◽  
Samuele Decarli ◽  
Lucas Mohn ◽  
Jun Sese ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Sequence Similarity ◽  
Ground Truth ◽  
Whole Genome ◽  
Initial Dataset ◽  
Quality Checks ◽  
Living Organisms ◽  
Set Up

Abstract Background Whole genome duplication (WGD) events are common in the evolutionary history of many living organisms. For decades, researchers have been trying to understand the genetic and epigenetic impact of WGD and its underlying molecular mechanisms. Particular attention was given to allopolyploid study systems, species resulting from an hybridization event accompanied by WGD. Investigating the mechanisms behind the survival of a newly formed allopolyploid highlighted the key role of DNA methylation. With the improvement of high-throughput methods, such as whole genome bisulfite sequencing (WGBS), an opportunity opened to further understand the role of DNA methylation at a larger scale and higher resolution. However, only a few studies have applied WGBS to allopolyploids, which might be due to lack of genomic resources combined with a burdensome data analysis process. To overcome these problems, we developed the Automated Reproducible Polyploid EpiGenetic GuIdance workflOw (ARPEGGIO): the first workflow for the analysis of epigenetic data in polyploids. This workflow analyzes WGBS data from allopolyploid species via the genome assemblies of the allopolyploid’s parent species. ARPEGGIO utilizes an updated read classification algorithm (EAGLE-RC), to tackle the challenge of sequence similarity amongst parental genomes. ARPEGGIO offers automation, but more importantly, a complete set of analyses including spot checks starting from raw WGBS data: quality checks, trimming, alignment, methylation extraction, statistical analyses and downstream analyses. A full run of ARPEGGIO outputs a list of genes showing differential methylation. ARPEGGIO was made simple to set up, run and interpret, and its implementation ensures reproducibility by including both package management and containerization. Results We evaluated ARPEGGIO in two ways. First, we tested EAGLE-RC’s performance with publicly available datasets given a ground truth, and we show that EAGLE-RC decreases the error rate by 3 to 4 times compared to standard approaches. Second, using the same initial dataset, we show agreement between ARPEGGIO’s output and published results. Compared to other similar workflows, ARPEGGIO is the only one supporting polyploid data. Conclusions The goal of ARPEGGIO is to promote, support and improve polyploid research with a reproducible and automated set of analyses in a convenient implementation. ARPEGGIO is available at https://github.com/supermaxiste/ARPEGGIO.

scholarly journals Extracellular matrix endocytosis in controlling matrix turnover and beyond: emerging roles in cancer

2016 ◽  
Vol 44 (5) ◽  
pp. 1347-1354 ◽  
Author(s):  
Elena Rainero
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Secreted Proteins ◽  
Oncogenic Transformation ◽  
Intracellular Degradation ◽  
Cell Functions ◽  
Ecm Degradation

The extracellular matrix (ECM) is a network of secreted proteins that, beyond providing support for tissues and organs, is involved in the regulation of a variety of cell functions, including cell proliferation, polarity, migration and oncogenic transformation. ECM homeostasis is maintained through a tightly controlled balance between synthesis, deposition and degradation. While the role of metalloproteases in ECM degradation is widely recognised, the contribution of ECM internalisation and intracellular degradation to ECM maintenance has been mostly overlooked. In this review, I will summarise what is known about the molecular mechanisms mediating ECM endocytosis and how this process impacts on diseases, such as fibrosis and cancer.

scholarly journals The Role of fnx1, a Fission Yeast Multidrug Resistance Protein, in the Transition of Cells to a Quiescent G0 State

1998 ◽  
Vol 18 (9) ◽  
pp. 5239-5246 ◽  
Author(s):  
Krassen Dimitrov ◽  
Shelley Sazer
Keyword(s):  
Multidrug Resistance ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Sequence Similarity ◽  
Cell Communication ◽  
Major Facilitator Superfamily ◽  
Natural Habitats ◽  
Resistance Protein ◽  
Major Facilitator

ABSTRACT Most microorganisms live in conditions of nutrient limitation in their natural habitats. When exposed to these conditions they respond with physiological and morphological changes that enable them to survive. To obtain insights into the molecular mechanisms of this response a systematic genetic screen was performed to identify genes that when overexpressed can induce a starvation-like response in the yeast species Schizosaccharomyces pombe. One gene that meets these criteria, fnx1 +, induces, transcriptionally correlates with, and is required for the entry into the quiescent G0 state that is normally induced by nitrogen starvation. fnx1 + encodes a protein with sequence similarity to the proton-driven plasma membrane transporters from the multidrug resistance group of the major facilitator superfamily of proteins. We propose that fnx1 +plays a role in the entry into G0, possibly by facilitating the release of a signaling substance into the environment as a means of cell-to-cell communication.

Abstract 35: Pseudo-knockin Mice Expressing JPH2-A399S Develop Cardiac Hypertrophy by Magnetic Resonance Imaging

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Ann P Quick ◽  
David L Beavers ◽  
Jordan Showell ◽  
Leonne E Philippen ◽  
Andrew P Landstrom ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Left Ventricular ◽  
Stress Markers ◽  
Septal Thickness ◽  
Septal Hypertrophy ◽  
Time Body Weight ◽  
Dependent Protein

Background: Dysfunctional intracellular Ca2+ handling has been implicated in adverse cardiac remodeling leading to hypertrophy and failure. Recent evidence has linked mutations in the Ca2+ handling protein Junctophilin-2 (JPH2) with the development of hypertrophic cardiomyopathy (HCM). However, the mechanism remains unknown. Objective: To use advanced in vivo imaging modalities in conjunction with biochemical techniques to determine the mechanism of hypertrophic remodeling in a murine model hosting a novel JPH2 mutation. Methods and Results: 1. Pseudo-knockin (PKI) Mice: transgenic mice with the JPH2-A399S mutation (or WT JPH2) containing inducible shJPH2 were dosed with tamoxifen to knock down the combined levels of JPH2 to near WT expression. 2. MRI: A399S and WT PKI controls were imaged at 2 months post injection at which time body weight was similar for mutants (29.8±.81g) and controls (31.8±1.29g). Intragate (Bruker) was used to obtain FLASH cine images and EKG-gated tagged images were obtained to determine strain. MRI post-processing and measurements were performed using Amira and Diagnosoft software. A399S PKI mice exhibited significantly increased left ventricular mass (2.96±.21g/kg; n=4) compared to controls (2.27±.08g/kg; n=3) and max diastolic septal thickness (1.39±.05mm; n=9 versus 0.97±.00mm; n=4; P<0.01). Mutants trended toward decreased septal strain (-8.97±1.04; n=4) compared to the control (-10.28; n=1) indicative of reduced regional contractility 3. Biochemistry: stress markers were measured by qPCR. Average BNP was increased over 3 fold. Larger sample size is needed to reach significance. Western blot showed no significant change (p=.78) in phosphorylated Ca2+/calmodulin-dependent protein kinase II, which is often activated by aberrant Ca2+ signaling. Conclusions: Our data show that the JPH2-A399S mutation leads to septal hypertrophy in PKI mice. This suggests that defects in JPH2 are sufficient to induce pathological cardiac remodeling. Despite the role of JPH2 in Ca2+ handling, this form of hypertrophy does not appear to be mediated by traditional Ca2+ signaling. Further studies will focus on alternative Ca2+-dependent pathways to elucidate the molecular mechanisms of these hypertrophic changes.

scholarly journals The Role of G Protein-Coupled Receptors (GPCRs) and Calcium Signaling in Schizophrenia. Focus on GPCRs Activated by Neurotransmitters and Chemokines

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1228
Author(s):  
Tomasz Boczek ◽  
Joanna Mackiewicz ◽  
Marta Sobolczyk ◽  
Julia Wawrzyniak ◽  
Malwina Lisek ◽  
...  
Keyword(s):  
G Protein ◽  
Psychiatric Illness ◽  
Antipsychotic Drugs ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
G Protein Coupled Receptors ◽  
Disease Development ◽  
Complex Picture ◽  
G Protein Coupled

Schizophrenia is a common debilitating disease characterized by continuous or relapsing episodes of psychosis. Although the molecular mechanisms underlying this psychiatric illness remain incompletely understood, a growing body of clinical, pharmacological, and genetic evidence suggests that G protein-coupled receptors (GPCRs) play a critical role in disease development, progression, and treatment. This pivotal role is further highlighted by the fact that GPCRs are the most common targets for antipsychotic drugs. The GPCRs activation evokes slow synaptic transmission through several downstream pathways, many of them engaging intracellular Ca2+ mobilization. Dysfunctions of the neurotransmitter systems involving the action of GPCRs in the frontal and limbic-related regions are likely to underly the complex picture that includes the whole spectrum of positive and negative schizophrenia symptoms. Therefore, the progress in our understanding of GPCRs function in the control of brain cognitive functions is expected to open new avenues for selective drug development. In this paper, we review and synthesize the recent data regarding the contribution of neurotransmitter-GPCRs signaling to schizophrenia symptomology.

scholarly journals Sesamin Protects Against Cardiac Remodeling Via Sirt3/ROS Pathway

2017 ◽  
Vol 44 (6) ◽  
pp. 2212-2227 ◽  
Author(s):  
Di Fan ◽  
Zheng Yang ◽  
Fang-yuan Liu ◽  
Ya-Ge Jin ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Protective Role ◽  
Control Group ◽  
Traditional Health ◽  
Smad2 Phosphorylation ◽  
Echocardiographic Parameters

Background/Aims: Cardiac remodeling is associated with oxidative stress. Sesamin, a well-known antioxidant from sesamin seeds, have been used extensively as traditional health foods. However, there is little known about the effect of sesamin on cardiac remodeling. Therefore, the present study aimed to determine whether sesamin could protect against cardiac remodeling and to clarify potential molecular mechanisms. Methods: The mice were subjected to either transverse aortic constriction (TAC) or sham surgery (control group). Beginning one week after surgery, the mice were oral gavage treated with sesamin (100mg·kg-1·day-1) or vehicle for 3 weeks. Cardiac hypertrophy was assessed by echocardiographic parameters, histological analyses and hypertrophic markers. Results: Sesamin alleviated cardiac hypertrophy, inhibited fibrosis and attenuated the inflammatory response. The increased production of reactive oxygen species, the activation of ERK1/2-dependent nuclear factor-κB and the increased level of Smad2 phosphorylation were observed in cardiac remolding model that were treated with sesamin. Furthermore, TAC induced alteration of Sirt3 and SOD2 was normalized by sesamin treatment. Finally, a selective Sirt3 inhibitor 3-TYP blocks all the protective role of sesamin, suggesting that a Sirt3-dependent effect of sesamin on cardiac remodeling. Conclusion: Sesamin improves cardiac function and prevents the development of cardiac hypertrophy via Sirt3/ROS pathway. Our results suggest the protective effect of sesamin on cardiac remolding.

scholarly journals Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases

2016 ◽  
Vol 310 (7) ◽  
pp. H802-H812 ◽  
Author(s):  
Bryan T. Hackfort ◽  
Paras K. Mishra
Keyword(s):  
Heart Failure ◽  
Hydrogen Sulfide ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
High Dose ◽  
Physiological Level ◽  
Cellular Processes ◽  
Regulatory Rnas ◽  
Apoptosis And Inflammation

Despite an obnoxious smell and toxicity at a high dose, hydrogen sulfide (H2S) is emerging as a cardioprotective gasotransmitter. H2S mitigates pathological cardiac remodeling by regulating several cellular processes including fibrosis, hypertrophy, apoptosis, and inflammation. These encouraging findings in rodents led to initiation of a clinical trial using a H2S donor in heart failure patients. However, the underlying molecular mechanisms by which H2S mitigates cardiac remodeling are not completely understood. Empirical evidence suggest that H2S may regulate signaling pathways either by directly influencing a gene in the cascade or interacting with nitric oxide (another cardioprotective gasotransmitter) or both. Recent studies revealed that H2S may ameliorate cardiac dysfunction by up- or downregulating specific microRNAs. MicroRNAs are noncoding, conserved, regulatory RNAs that modulate gene expression mostly by translational inhibition and are emerging as a therapeutic target for cardiovascular disease (CVD). Few microRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new avenue for exploring the H2S-microRNA crosstalk in CVD. This review embodies regulatory mechanisms that maintain the physiological level of H2S, exogenous H2S donors used for increasing the tissue levels of H2S, H2S-mediated regulation of CVD, H2S-microRNAs crosstalk in relation to the pathophysiology of heart disease, clinical trials on H2S, and future perspectives for H2S as a therapeutic agent for heart failure.

scholarly journals Current State and Progress of Research on the Role of lncRNA in HBV-Related Liver Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xueke Wang ◽  
Meisong Kang ◽  
Chun Liu ◽  
Ting Lin ◽  
Xiao Han ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Tumor Suppressor Genes ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Sequencing Technology ◽  
Regulatory Pathways ◽  
Current State ◽  
B Virus

Hepatocellular carcinoma (HCC) is a malignant tumor with the highest mortality rate in the world, and hepatitis B virus (HBV) plays an important role in its development. Long noncoding RNA (lncRNA) is highly related to the inactivation of tumor suppressor genes and the activation of oncogenes in HCC. Researchers have used high-throughput sequencing technology to identify many noncoding transcripts related to the development of HCC and have studied the interaction between these transcripts and DNA, RNA, or protein to determine the relevant mechanism in the development of HCC. In general, the research on lncRNA represents a new field of cancer research, and the imbalance in lncRNA plays an pivotal role in the occurrence of liver cancer. In this review, we summarize some of the dysfunctional lncRNAs in human HCC associated with HBV infection. Their regulatory pathways, functions, and potential molecular mechanisms in the occurrence and development of HCC are discussed.

Sign in / Sign up

Export Citation Format

Share Document