scholarly journals The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

2021 ◽  
Vol 14 (2) ◽  
pp. 96
Author(s):  
Susie L. Brown ◽  
Samantha Kendrick
Keyword(s):  
Gene Expression ◽  
Secondary Structure ◽  
Biological Function ◽  
Molecular Target ◽  
Therapeutic Approaches ◽  
Promoter Regions ◽  
New Therapeutic Approaches ◽  
G Quadruplex ◽  
Dna Elements ◽  
Insight Into

Stretches of cytosine-rich DNA are capable of adopting a dynamic secondary structure, the i-motif. When within promoter regions, the i-motif has the potential to act as a molecular switch for controlling gene expression. However, i-motif structures in genomic areas of repetitive nucleotide sequences may play a role in facilitating or hindering expansion of these DNA elements. Despite research on the i-motif trailing behind the complementary G-quadruplex structure, recent discoveries including the identification of a specific i-motif antibody are pushing this field forward. This perspective reviews initial and current work characterizing the i-motif and providing insight into the biological function of this DNA structure, with a focus on how the i-motif can serve as a molecular target for developing new therapeutic approaches to modulate gene expression and extension of repetitive DNA.

Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression

2021 ◽  
Author(s):  
Jaroslav Malina ◽  
Hana Kostrhunova ◽  
Nicholas Patrick Farrell ◽  
Viktor Brabec
Keyword(s):  
Gene Expression ◽  
Drug Targets ◽  
Platinum Complexes ◽  
Anticancer Therapy ◽  
Promoter Regions ◽  
Quadruplex Dna ◽  
G Quadruplex

DNA G-quadruplex (G4) structures formed in the telomeric and promoter regions represent attractive drug targets for anticancer therapy. Thus, much effort has been devoted to the development of a variety...

scholarly journals Dynamics Studies of DNA with Non-canonical Structure Using NMR Spectroscopy

2020 ◽  
Vol 21 (8) ◽  
pp. 2673 ◽  
Author(s):  
Kwang-Im Oh ◽  
Jinwoo Kim ◽  
Chin-Ju Park ◽  
Joon-Hwa Lee
Keyword(s):  
Nmr Spectroscopy ◽  
Biological Function ◽  
Conformational Exchange ◽  
Biological Processes ◽  
Dynamic Characterization ◽  
Dynamic Features ◽  
Dna Structures ◽  
Left Handed ◽  
G Quadruplex ◽  
Insight Into

The non-canonical structures of nucleic acids are essential for their diverse functions during various biological processes. These non-canonical structures can undergo conformational exchange among multiple structural states. Data on their dynamics can illustrate conformational transitions that play important roles in folding, stability, and biological function. Here, we discuss several examples of the non-canonical structures of DNA focusing on their dynamic characterization by NMR spectroscopy: (1) G-quadruplex structures and their complexes with target proteins; (2) i-motif structures and their complexes with proteins; (3) triplex structures; (4) left-handed Z-DNAs and their complexes with various Z-DNA binding proteins. This review provides insight into how the dynamic features of non-canonical DNA structures contribute to essential biological processes.

scholarly journals How to Improve the Antioxidant Defense in Asphyxiated Newborns—Lessons from Animal Models

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 898
Author(s):  
Hanna Kletkiewicz ◽  
Maciej Klimiuk ◽  
Alina Woźniak ◽  
Celestyna Mila-Kierzenkowska ◽  
Karol Dokladny ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Animal Models ◽  
Iron Chelation ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Protective Capacity ◽  
Neonatal Asphyxia ◽  
New Therapeutic Approaches ◽  
The Brain ◽  
Insight Into

Oxygen free radicals have been implicated in brain damage after neonatal asphyxia. In the early phase of asphyxia/reoxygenation, changes in antioxidant enzyme activity play a pivotal role in switching on and off the cascade of events that can kill the neurons. Hypoxia/ischemia (H/I) forces the brain to activate endogenous mechanisms (e.g., antioxidant enzymes) to compensate for the lost or broken neural circuits. It is important to evaluate therapies to enhance the self-protective capacity of the brain. In animal models, decreased body temperature during neonatal asphyxia has been shown to increase cerebral antioxidant capacity. However, in preterm or severely asphyxiated newborns this therapy, rather than beneficial seems to be harmful. Thus, seeking new therapeutic approaches to prevent anoxia-induced complications is crucial. Pharmacotherapy with deferoxamine (DFO) is commonly recognized as a beneficial regimen for H/I insult. DFO, via iron chelation, reduces oxidative stress. It also assures an optimal antioxidant protection minimizing depletion of the antioxidant enzymes as well as low molecular antioxidants. In the present review, some aspects of recently acquired insight into the therapeutic effects of hypothermia and DFO in promoting neuronal survival after H/I are discussed.

Insights of potential G-quadruplex sequences in telomeres and proto-oncogenes

2013 ◽  
Vol 21 (3-4) ◽  
pp. 118-124 ◽  
Author(s):  
Rajendra Bhadane ◽  
Rupali Bhadane ◽  
Dhananjay Meshram
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Binding Proteins ◽  
Promoter Regions ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
G Quadruplex ◽  
Anticancer Target ◽  
Stable Structures

Guanine rich sequences have the ability to fold into stable 4 stranded structures called G-quadruplex under physiological concentrations of Na+ or K+. G-quadruplexes are found in telomeres, being stable structures under the control of telomerase binding proteins. They are also identified throughout the genome and are enriched in promoter regions of protein coding genes, upstream and downstream of the transcription initiation sites. A number of these promoter quadruplexes have been investigated for several proto-oncogenes. The formation of these quadruplexes can lead to chemical intervention of gene expression using a G-quadruplex binding ligand. We review location, configuration, and stabilization of these quadruplexes in some of the important promoters with regards to their potential as anticancer target.

scholarly journals The functional relationship of the interleukins.

1980 ◽  
Vol 151 (6) ◽  
pp. 1551-1556 ◽  
Author(s):  
K A Smith ◽  
L B Lachman ◽  
J J Oppenheim ◽  
M F Favata
Keyword(s):  
T Cell ◽  
Functional Relationship ◽  
Immunosuppressive Agents ◽  
Therapeutic Approaches ◽  
Disease States ◽  
New Therapeutic Approaches ◽  
Relationship Of ◽  
Insight Into ◽  
T Cell Growth Factor ◽  
Stimulation Of

The mechanism of the lymphoproliferative effect of the macrophage product lymphocyte-activating factor [LAF(IL1] appears to be mediated by the stimulation of the release of T cell growth factor [TCGF(IL2)] by T cells. The magnitude of the resultant T cell proliferative clonal expansion is thus dependent upon the quantity of both LAF(IL1) and TCGF(IL2) induced by antigen or lectin stimulation. These observations, coupled with the ability to measure the production and actions of these hormone-like lymphokines, should allow for increased insight into the mode of action of immunoenhancing and immunosuppressive agents, as well as for new therapeutic approaches to disease states involving T lymphocytes.

Adiponectin Synthesis, Secretion and Extravasation from Circulation to Interstitial Space

Physiology ◽  
2021 ◽  
Vol 36 (3) ◽  
pp. 134-149 ◽  
Author(s):  
Simone C. da Silva Rosa ◽  
Meilian Liu ◽  
Gary Sweeney
Keyword(s):  
Gene Expression ◽  
Interstitial Space ◽  
Therapeutic Interventions ◽  
Physiological Effects ◽  
Adiponectin Gene ◽  
Therapeutic Approaches ◽  
Cellular Models ◽  
Regulatory Aspects ◽  
Critical Insight ◽  
Insight Into

Adiponectin, an adipokine that circulates as multiple multimeric complexes at high levels in serum, has antidiabetic, anti-inflammatory, antiatherogenic, and cardioprotective properties. Understanding the mechanisms regulating adiponectin’s physiological effects is likely to provide critical insight into the development of adiponectin-based therapeutics to treat various metabolic-related diseases. In this review, we summarize our current understanding on adiponectin action in its various target tissues and in cellular models. We also focus on recent advances in two particular regulatory aspects; namely, the regulation of adiponectin gene expression, multimerization, and secretion, as well as extravasation of circulating adiponectin to the interstitial space and its degradation. Finally, we discuss some potential therapeutic approaches using adiponectin as a target and the current challenges facing adiponectin-based therapeutic interventions.

scholarly journals Toward a unified theory of aging and regeneration

2019 ◽  
Vol 14 (9) ◽  
pp. 867-886 ◽  
Author(s):  
Michael D West ◽  
Hal Sternberg ◽  
Ivan Labat ◽  
Jeffrey Janus ◽  
Karen B Chapman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tissue Regeneration ◽  
Antagonistic Pleiotropy ◽  
Unified Theory ◽  
Degenerative Diseases ◽  
Therapeutic Approaches ◽  
Regenerative Capacity ◽  
New Therapeutic Approaches ◽  
Age Related ◽  
Theory Of Aging

Growing evidence supports the antagonistic pleiotropy theory of mammalian aging. Accordingly, changes in gene expression following the pluripotency transition, and subsequent transitions such as the embryonic–fetal transition, while providing tumor suppressive and antiviral survival benefits also result in a loss of regenerative potential leading to age-related fibrosis and degenerative diseases. However, reprogramming somatic cells to pluripotency demonstrates the possibility of restoring telomerase and embryonic regeneration pathways and thus reversing the age-related decline in regenerative capacity. A unified model of aging and loss of regenerative potential is emerging that may ultimately be translated into new therapeutic approaches for establishing induced tissue regeneration and modulation of the embryo-onco phenotype of cancer.

scholarly journals Photosensitizers Based on G-Quadruplex Ligand for Cancer Photodynamic Therapy

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1340
Author(s):  
Keiko Kawauchi ◽  
Ryoto Urano ◽  
Natsuki Kinoshita ◽  
Shin Kuwamoto ◽  
Takeru Torii ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Secondary Structure ◽  
Molecular Target ◽  
Untranslated Regions ◽  
Reactive Oxidative Species ◽  
Dna And Rna ◽  
Porphyrin Derivatives ◽  
G Quadruplex ◽  
Novel Strategy ◽  
Oxidative Species

G-quadruplex (G4) is the non-canonical secondary structure of DNA and RNA formed by guanine-rich sequences. G4-forming sequences are abundantly located in telomeric regions and in the promoter and untranslated regions (UTR) of cancer-related genes, such as RAS and MYC. Extensive research has suggested that G4 is a potential molecular target for cancer therapy. Here, we reviewed G4 ligands as photosensitizers for cancer photodynamic therapy (PDT), which is a minimally invasive therapeutic approach. The photosensitizers, such as porphyrins, were found to be highly toxic against cancer cells via the generation of reactive oxidative species (ROS) upon photo-irradiation. Several porphyrin derivatives and analogs, such as phthalocyanines, which can generate ROS upon photo-irradiation, have been reported to act as G4 ligands. Therefore, they have been implicated as promising photosensitizers that can selectively break down cancer-related DNA and RNA forming G4. In this review, we majorly focused on the potential application of G4 ligands as photosensitizers, which would provide a novel strategy for PDT, especially molecularly targeted PDT (mtPDT).

scholarly journals Werner syndrome helicase modulates G4 DNA-dependent transcription and opposes mechanistically distinct senescence-associated gene expression programs

2015 ◽  
Author(s):  
Weiliang Tang ◽  
Ana I. Robles ◽  
Richard P. Beyer ◽  
Lucas T. Gray ◽  
Giang Hong Nguyen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Stability ◽  
Werner Syndrome ◽  
Premature Aging ◽  
Dna Motifs ◽  
Trna Synthetases ◽  
Over Expression ◽  
G4 Dna ◽  
G Quadruplex ◽  
Insight Into

Werner syndrome (WS) is a prototypic heritable adult human progeroid syndrome in which signs of premature aging are associated with genetic instability and an elevated risk of specific types of cancer. We have quantified mRNA and microRNA (miRNA) expression in WS patient fibroblasts, and in WRN-depleted fibroblasts. Genes down-regulated in WS patient fibroblasts were highly enriched in G-quadruplex (G4) DNA motifs. The strength, location and strand specificity of this association provide strong experimental evidence that G4 motifs or motif-dependent G-quadruplexes are bound by WRN in human cells to modulate gene expression. The expression of many miRNAs was perturbed by loss of WRN function. WRN depletion altered the expression of >500 miRNAs. miRNAs linked to cell signaling, genome stability assurance and tumorigenesis were among the small number of these miRNAs that were persistently altered in WS patient fibroblasts. An unexpected and highly distinct finding in WS cells was the coordinate over-expression of nearly all cytoplasmic tRNA synthetases and their associated AIMP proteins. Our results provide new insight into WS pathogenesis, and identify therapeutically accessible mechanisms that may drive disease pathogenesis in WS and in the general population.

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