scholarly journals The molecular mechanisms of multidrug resistance of human glioblastomas

2021 ◽  
Vol 67 (1) ◽  
pp. 20-28
Author(s):  
Alexandr Chernov ◽  
Irina Baldueva ◽  
Tatyana Nekhaeva ◽  
Elvira Galimova ◽  
Diana Alaverdian ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Drug Resistance ◽  
Transcription Factors ◽  
Growth Factors ◽  
Multidrug Resistance ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Polymorphic Variants ◽  
Signal Transduction Proteins

In review discusses the phenomenon of drug resistance of GB in the context of the expression of ABC family transporter proteins and the processes of proliferation, angiogenesis, recurrence and death. The emphasis is on the identifying for molecular targets among growth factors, receptors, signal transduction proteins, microRNAs, transcription factors, proto-oncogenes, tumor suppressor genes and their polymorphic variants (SNPs) for the development and creation of targeted anticancer drugs.

scholarly journals Divergence in Coding Sequence and Expression of Different Functional Categories of Immune Genes between Two Wild Rodent Species

2021 ◽  
Vol 13 (3) ◽  
Author(s):  
Xiuqin Zhong ◽  
Max Lundberg ◽  
Lars Råberg
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Immune Function ◽  
Sequence Divergence ◽  
Expression Divergence ◽  
Functional Categories ◽  
Coding Sequence ◽  
Immune Genes ◽  
Genes Encoding ◽  
Signal Transduction Proteins

Abstract Differences in immune function between species could be a result of interspecific divergence in coding sequence and/or expression of immune genes. Here, we investigate how the degree of divergence in coding sequence and expression differs between functional categories of immune genes, and if differences between categories occur independently of other factors (expression level, pleiotropy). To this end, we compared spleen transcriptomes of wild-caught yellow-necked mice and bank voles. Immune genes expressed in the spleen were divided into four categories depending on the function of the encoded protein: pattern recognition receptors (PRR); signal transduction proteins; transcription factors; and cyto- and chemokines and their receptors. Genes encoding PRR and cyto-/chemokines had higher sequence divergence than genes encoding signal transduction proteins and transcription factors, even when controlling for potentially confounding factors. Genes encoding PRR also had higher expression divergence than genes encoding signal transduction proteins and transcription factors. There was a positive correlation between expression divergence and coding sequence divergence, in particular for PRR genes. We propose that this is a result of that divergence in PRR coding sequence leads to divergence in PRR expression through positive feedback of PRR ligand binding on PRR expression. When controlling for sequence divergence, expression divergence of PRR genes did not differ from other categories. Taken together, the results indicate that coding sequence divergence of PRR genes is a major cause of differences in immune function between species.

scholarly journals Targeting extracellular matrix remodeling in disease: Could resveratrol be a potential candidate?

2016 ◽  
Vol 242 (4) ◽  
pp. 374-383 ◽  
Author(s):  
Renu Agarwal ◽  
Puneet Agarwal
Keyword(s):  
Extracellular Matrix ◽  
Transcription Factors ◽  
Growth Factors ◽  
Molecular Targets ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Matrix Deposition ◽  
Mitogen Activated Protein ◽  
Extracellular Matrix Deposition

Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.

scholarly journals Use of Transcriptomic Analyses to Elucidate the Mechanism Governing Nodal Root Development in Eremochloa ophiuroides (Munro) Hack.

2021 ◽  
Vol 12 ◽  
Author(s):  
Rui Wang ◽  
Haoyan Zhao ◽  
Hailin Guo ◽  
Junqin Zong ◽  
Jianjian Li ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Root Development ◽  
Molecular Mechanisms ◽  
Homologous Gene ◽  
Root Tips ◽  
Rooting Ability ◽  
Nodal Roots ◽  
Nodal Root ◽  
Eremochloa Ophiuroides

Centipedegrass [Eremochloa ophiuroides (Munro) Hack.] is a perennial warm-season grass that originated in China, and its speed of nodal rooting is important for lawn establishment. In our study, centipedegrass nodal rooting ability was limited by node aging. Transcriptome sequencing of nodal roots after 0, 2, 4, and 8 days of water culture was performed to investigate the molecular mechanisms of root development. GO enrichment and KEGG pathway analyses of DEGs indicated that plant hormone signal transduction and transcription factors might play important roles in centipedegrass nodal root growth. Among them, E3 ubiquitin-protein ligases participated in multiple hormone signal transduction pathways and interacted with transcription factors. Furthermore, an E3 ubiquitin protein ligase EoSINAT5 overexpressed in rice resulted in longer roots and more numerous root tips, while knockout of LOC_Os07g46560 (the homologous gene of EoSINAT5 in rice) resulted in shorter roots and fewer root tips. These results indicated that EoSINAT5 and its homologous gene are able to promote nodal root development. This research presents the transcriptomic analyses of centipedegrass nodal roots, and may contribute to elucidating the mechanism governing the development of nodal roots and facilitates the use of molecular breeding in improving rooting ability.

scholarly journals An Efficient Method to Identify Conditionally Activated Transcription Factors and their Corresponding Signal Transduction Pathway Segments

2009 ◽  
Vol 3 ◽  
pp. BBI.S3485
Author(s):  
Haiyan Hu
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Efficient Method ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Protein Interaction Data ◽  
Transduction Pathway ◽  
Binding Data ◽  
Microarray Datasets

A signal transduction pathway (STP) is a cascade composed of a series of signal transferring steps, which often activate one or more transcription factors (TFs) to control the transcription of target genes. Understanding signaling pathways is important to our understanding of the molecular mechanisms of disease. Many condition-annotated pathways have been deposited in public databases. However, condition-annotated pathways are far from complete, considering the large number of possible conditions. Computational methods to assist in the identification of conditionally activated pathways are greatly needed. In this paper, we propose an efficient method to identify conditionally activated pathway segments starting from the identification of conditionally activated TFs, by incorporating protein-DNA binding data, gene expression data and protein interaction data. Applying our methods on several microarray datasets, we have discovered many significantly activated TFs and their corresponding pathway segments, which are supported by evidence in the literature.

scholarly journals Mitochondrial dysfunctions trigger the calcium signaling-dependent fungal multidrug resistance

2019 ◽  
Vol 117 (3) ◽  
pp. 1711-1721 ◽  
Author(s):  
Yeqi Li ◽  
Yuanwei Zhang ◽  
Chi Zhang ◽  
Hongchen Wang ◽  
Xiaolei Wei ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Mitochondrial Dysfunction ◽  
Calcium Signaling ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Drug Binding ◽  
Fitness Cost ◽  
Drug Resistant ◽  
Resistant Mutants

Drug resistance in fungal pathogens has risen steadily over the past decades due to long-term azole therapy or triazole usage in agriculture. Modification of the drug target protein to prevent drug binding is a major recognized route to induce drug resistance. However, mechanisms for nondrug target-induced resistance remain only loosely defined. Here, we explore the molecular mechanisms of multidrug resistance resulted from an efficient adaptation strategy for survival in drug environments in the human pathogen Aspergillus fumigatus. We show that mutants conferring multidrug resistance are linked with mitochondrial dysfunction induced by defects in heme A biosynthesis. Comparison of the gene expression profiles between the drug-resistant mutants and the parental wild-type strain shows that multidrug-resistant transporters, chitin synthases, and calcium-signaling-related genes are significantly up-regulated, while scavenging mitochondrial reactive oxygen species (ROS)-related genes are significantly down-regulated. The up-regulated-expression genes share consensus calcium-dependent serine threonine phosphatase-dependent response elements (the binding sites of calcium-signaling transcription factor CrzA). Accordingly, drug-resistant mutants show enhanced cytosolic Ca2+ transients and persistent nuclear localization of CrzA. In comparison, calcium chelators significantly restore drug susceptibility and increase azole efficacy either in laboratory-derived or in clinic-isolated A. fumigatus strains. Thus, the mitochondrial dysfunction as a fitness cost can trigger calcium signaling and, therefore, globally up-regulate a series of embedding calcineurin-dependent–response-element genes, leading to antifungal resistance. These findings illuminate how fitness cost affects drug resistance and suggest that disruption of calcium signaling might be a promising therapeutic strategy to fight against nondrug target-induced drug resistance.

scholarly journals MOLECULAR MECHANISMS OF MULTIDRUG RESISTANCE OVERCOMING BY LIPOSOMAL ANTITUMOR DRUGS

2015 ◽  
Vol 14 (1) ◽  
pp. 3-10 ◽  
Author(s):  
M. A. Baryshnikova ◽  
A. Yu. Baryshnikov ◽  
D. A. Afanasieva
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Molecular Mechanisms ◽  
Liposomal Doxorubicin ◽  
Gene Activation ◽  
Antitumor Drugs ◽  
Liposomal Drug ◽  
P Glycoprotein ◽  
Fas Signaling ◽  
Apoptosis Gene

The liposomal antitumor drugs cell death induction mechanism has been analyzed in this work. Liposomal dosage forms of doxorubicin, cisplatin and aranosa overcome drug resistance. However, the mechanism of overcoming drug resistance by this drugs is different. Liposomal doxorubicin overcomes multidrug resistance by liposomes binding with the P-glycoprotein in 185 position of glycine. Liposomal cisplatin overcomes monoresistance by external apoptosis gene activation. The liposomal aranosa does not use CD95/Fas signaling pathway of apoptosis. Thus, liposomal drug action mechanism depends on the type of cells, and on the antitumor drug, that is enclosed in a liposome and can be individualized in each case.

A Review on Regulation of Gene in Eukaryotes

2016 ◽  
Vol 5 (08) ◽  
pp. 4729 ◽  
Author(s):  
Sasmita Panda
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcription Factors ◽  
Growth Factors ◽  
Environmental Factors ◽  
Dna Sequences ◽  
Hormone Receptors

Gene expression in eukaryotes can be induced by environmental factors like heat and light and by chemical molecules such as hormones and growth factors. Hormone- induced gene expression is mediated by proteins that interact with the hormones. Some of these hormone receptors act directly as transcription factors by binding to DNA sequences in the vicinity of a gene; others control transcription indirectly through a signal transduction path way that targets transcription factors to a gene.

Transcription Factors as Molecular Targets: Molecular Mechanisms of Decoy ODN and their Design

2003 ◽  
Vol 4 (8) ◽  
pp. 603-608 ◽  
Author(s):  
Naruya Tomita ◽  
Toshio Ogihara ◽  
Ryuichi Morishita
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Molecular Targets

Arteriogenesis: A focus on signal transduction cascades and transcription factors

2007 ◽  
Vol 98 (11) ◽  
pp. 940-943 ◽  
Author(s):  
Elisabeth Deindl
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Rho Kinase ◽  
Early Growth Response ◽  
Collateral Artery ◽  
Early Growth Response 1 ◽  
Serum Response ◽  
Increased Blood Flow

SummaryIn recent years intensive investigations have been performed to unravel the molecular mechanisms of collateral artery growth (arteriogenesis), a process designed by nature to compensate the devastating consequences of major arterial occlusions. Currently, a variety of gene products as well as signal transduction pathways involved in arteriogenesis have been identified. However, it is still not clear how the progression of cellular signals evoked by an increased blood flow and therefore mechanical stress proceeds. Literature research identified the transcription factors early growth response-1 (Egr-1) as well as serum response factor (SRF) and myocardin-related transcription factors (MRTFs) as liaisons connecting the key pathways of arteriogenesis, i.e.the Rho-kinase pathway and the MEK/ERK pathway, with each other as well as with downstream genes.

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