scholarly journals Rethinking the bioavailability and cellular transport properties of S-adenosylmethionine

Cell Stress ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 1-5
Author(s):  
Yudong Sun ◽  
Jason W. Locasale
Keyword(s):  
Gene Expression ◽  
Plasma Membrane ◽  
Transport Properties ◽  
Therapeutic Potential ◽  
Cellular Transport ◽  
Over The Counter ◽  
Cellular Processes ◽  
Nutrient Supplement ◽  
Wide Range ◽  
Cellular Permeability

S-adenosylmethionine (SAM) is a versatile metabolite that participates in a wide range of reactions such as methylation and transsulfuration. These capabilities allow SAM to influence cellular processes such as gene expression and redox balancing. The importance of SAM is highlighted by its widespread usage as an over-the-counter nutrient supplement and as an experimental reagent in molecular biology. The bioavailability and cellular transport properties of SAM, however, are often overlooked under these contexts, putting limits on SAM’s therapeutic potential and complicating the interpretation of experimental results. In this article, we examined the chemical stability and cellular permeability of SAM, proposed a schematic for indirect SAM transport across the mammalian plasma membrane, and lastly discussed the implications arising from such transport schematic.

scholarly journals Identification of anN-Acetylglucosamine Transporter That Mediates Hyphal Induction inCandida albicans

2007 ◽  
Vol 18 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Francisco J. Alvarez ◽  
James B. Konopka
Keyword(s):  
Plasma Membrane ◽  
Hyphal Growth ◽  
Nutrient Sensing ◽  
Major Facilitator Superfamily ◽  
Cellular Processes ◽  
Macrophage Phagocytosis ◽  
Wide Range ◽  
High Concentrations ◽  
Hyphal Formation ◽  
Major Facilitator

The sugar N-acetylglucosamine (GlcNAc) plays an important role in nutrient sensing and cellular regulation in a wide range of organisms from bacteria to humans. In the fungal pathogen Candida albicans, GlcNAc induces a morphological transition from budding to hyphal growth. Proteomic comparison of plasma membrane proteins from buds and from hyphae induced by GlcNAc identified a novel hyphal protein (Ngt1) with similarity to the major facilitator superfamily of transporters. An Ngt1-GFP fusion was detected in the plasma membrane after induction with GlcNAc, but not other related sugars. Ngt1-GFP was also induced by macrophage phagocytosis, suggesting a role for the GlcNAc response in signaling entry into phagolysosomes. NGT1 is needed for efficient GlcNAc uptake and for the ability to induce hyphae at low GlcNAc concentrations. High concentrations of GlcNAc could bypass the need for NGT1 to induce hyphae, indicating that elevated intracellular levels of GlcNAc induce hyphal formation. Expression of NGT1 in Saccharomyces cerevisiae promoted GlcNAc uptake, indicating that Ngt1 acts directly as a GlcNAc transporter. Transport mediated by Ngt1 was specific, as other sugars could not compete for the uptake of GlcNAc. Thus, Ngt1 represents the first eukaryotic GlcNAc transporter to be discovered. The presence of NGT1 homologues in the genome sequences of a wide range of eukaryotes from yeast to mammals suggests that they may also function in the cellular processes regulated by GlcNAc, including those that underlie important diseases such as cancer and diabetes.

scholarly journals Targeting RNA structures in diseases with small molecules

2020 ◽  
Vol 64 (6) ◽  
pp. 955-966 ◽  
Author(s):  
Yanqiu Shao ◽  
Qiangfeng Cliff Zhang
Keyword(s):  
Gene Expression ◽  
Molecular Biology ◽  
Small Molecules ◽  
Structural Biology ◽  
Rna Structure ◽  
Therapeutic Potential ◽  
Rna Structures ◽  
Gene Expression And Regulation ◽  
Cellular Processes ◽  
Target Rna

Abstract RNA is crucial for gene expression and regulation. Recent advances in understanding of RNA biochemistry, structure and molecular biology have revealed the importance of RNA structure in cellular processes and diseases. Various approaches to discovering drug-like small molecules that target RNA structure have been developed. This review provides a brief introduction to RNA structural biology and how RNA structures function as disease regulators. We summarize approaches to targeting RNA with small molecules and highlight their advantages, shortcomings and therapeutic potential.

scholarly journals The Arabidopsis SAC9 Enzyme defines a cortical population of early endosomes and restricts PI(4,5)P2 to the Plasma Membrane

2021 ◽  
Author(s):  
Mehdi Doumane ◽  
Alexis Lebecq ◽  
Aurelie Fangain ◽  
Vincent Bayle ◽  
Frederique Rozier ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Cortex ◽  
Cellular Processes ◽  
Phosphoinositide Phosphatase ◽  
Early Endosomes ◽  
Wide Range ◽  
Intracellular Compartments ◽  
Functional Consequences ◽  
Src Homology ◽  
Golgi Network

Membranes lipids, and especially phosphoinositides, are differentially enriched within the eukaryotic endomembrane system. This generates a landmark code by modulating the properties of each membrane. Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] specifically accumulates at the plasma membrane in yeast, animal and plant cells, where it regulates a wide range of cellular processes including endocytosis. However, the functional consequences of mispatterning PI(4,5)P2 in plants are unknown. Here, we functionally characterized the phosphoinositide phosphatase SUPPRESSOR OF ACTIN9 (SAC9) in Arabidopsis thaliana (Arabidopsis). We found that SAC9 depletion led to the ectopic localization of PI(4,5)P2 on cortical intracellular compartments, which depends on PI4P and PI(4,5)P2 production at the plasma membrane. SAC9 localizes to a subpopulation of trans-Golgi Network/early endosomes that are spatially restricted to a region close to the cell cortex and that are coated with clathrin. Furthermore, it interacts and colocalizes with the endocytic component Src Homology 3 Domain Protein 2 (SH3P2). In the absence of SAC9, SH3P2 localization is altered and the clathrin mediated endocytosis rate is significantly reduced. Thus, SAC9 is required to maintain efficient endocytic uptake, highlighting the importance of restricting the PI(4,5)P2 pool at the plasma membrane for the proper regulation of endocytosis in plants.

scholarly journals The Streptococcus pyogenes signaling peptide SpoV regulates streptolysin O and enhances survival in murine blood

2021 ◽  
Author(s):  
Andrea L. Herrera ◽  
Eduardo A. Callegari ◽  
Michael S. Chaussee
Keyword(s):  
Gene Expression ◽  
Streptococcus Pyogenes ◽  
Regulatory Networks ◽  
Environmental Changes ◽  
Therapeutic Potential ◽  
Transcript Abundance ◽  
Bacterial Survival ◽  
Streptolysin O ◽  
Wide Range ◽  
Peptide Derivatives

Streptococcus pyogenes (Group A Streptococcus, GAS) is a human pathogen that causes a wide range of diseases. For successful colonization within a variety of host niches, GAS must sense and respond to environmental changes. Intercellular communication mediated by peptides is one way GAS coordinates gene expression in response to diverse environmental stressors, which enhances bacterial survival and contributes to virulence. Using peptidomics we identified SpoV (Streptococcal peptide controlling virulence) in culture supernatant fluids. SpoV is a secreted peptide encoded near the gene encoding the extracellular cholesterol-dependent cytolysin streptolysin O (slo). The addition of synthetic SpoV peptide derivatives, but not control peptides, increased slo transcript abundance in an M49 isolate but not in an M3 isolate. Deletion of spoV decreased slo transcript abundance, extracellular SLO protein levels, and SLO-specific hemolytic activity. Complementation of the spoV mutant increased slo transcript abundance. Lastly, a spoV mutant was deficient in the ability to survive in murine blood compared to the parental strain. Moreover, pre-incubation of the spoV mutant with synthetic SpoV peptide derivatives increased GAS survival. Our findings show that slo expression is regulated, in part, by the GAS-specific signaling peptide SpoV. IMPORTANCE GAS secretes signaling peptides that can alter gene expression and impact virulence. We used peptidomics to identify a signaling peptide designated SpoV. Further, we showed that SpoV altered the expression of the cholesterol-dependent cytolysin SLO. Peptide signaling plays an important regulatory role during disease progression among several bacterial pathogens, including GAS. The therapeutic potential of manipulating peptide-controlled regulatory networks is an attractive option for the development of novel therapeutic strategies that disrupt virulence gene expression.

scholarly journals The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2238
Author(s):  
Artem Nedoluzhko ◽  
Natalia Gruzdeva ◽  
Fedor Sharko ◽  
Sergey Rastorguev ◽  
Natalia Zakharova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cellular Processes ◽  
Non Coding Rna

Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.

scholarly journals Implications of FBXW7 in Neurodevelopment and Neurodegeneration: Molecular Mechanisms and Therapeutic Potential

2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Yang ◽  
Xuan Zhou ◽  
Xinpeng Liu ◽  
Ruying Song ◽  
Yiming Gao ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Ubiquitin Proteasome System ◽  
Cellular Protein ◽  
Protein Homeostasis ◽  
Potential Therapeutic Target ◽  
Cellular Processes ◽  
Wide Range ◽  
Ubiquitin Proteasome

The ubiquitin-proteasome system (UPS) mediated protein degradation is crucial to maintain quantitive and functional homeostasis of diverse proteins. Balanced cellular protein homeostasis controlled by UPS is fundamental to normal neurological functions while impairment of UPS can also lead to some neurodevelopmental and neurodegenerative disorders. Functioning as the substrate recognition component of the SCF-type E3 ubiquitin ligase, FBXW7 is essential to multiple aspects of cellular processes via targeting a wide range of substrates for proteasome-mediated degradation. Accumulated evidence shows that FBXW7 is fundamental to neurological functions and especially implicated in neurodevelopment and the nosogenesis of neurodegeneration. In this review, we describe general features of FBXW7 gene and proteins, and mainly present recent findings that highlight the vital roles and molecular mechanisms of FBXW7 in neurodevelopment such as neurogenesis, myelination and cerebral vasculogenesis and in the pathogenesis of some typical neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Additionally, we also provide a prospect on focusing FBXW7 as a potential therapeutic target to rescue neurodevelopmental and neurodegenerative impairment.

scholarly journals The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7109
Author(s):  
Priti Tagde ◽  
Pooja Tagde ◽  
Fahadul Islam ◽  
Sandeep Tagde ◽  
Muddaser Shah ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Review Article ◽  
Biological Pathways ◽  
Therapeutic Benefits ◽  
Anticancer Effects ◽  
Wide Range ◽  
Cellular Permeability ◽  
Chronic Disorders ◽  
Viable Method

Curcumin is the primary polyphenol in turmeric’s curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin’s bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.

vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

1990 ◽  
Vol 48 (3) ◽  
pp. 330-331
Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Chick Embryo ◽  
Basement Membrane ◽  
Sem Images ◽  
Intimate Contact ◽  
Cellular Processes ◽  
Sem Study ◽  
Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

Isoform-Selective PI3K Inhibitors for Various Diseases

2020 ◽  
Vol 20 (12) ◽  
pp. 1074-1092 ◽  
Author(s):  
Rammohan R.Y. Bheemanaboina
Keyword(s):  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Type I ◽  
Selective Inhibitors ◽  
Pi3k Inhibitors ◽  
Wide Range ◽  
Lipid Kinases ◽  
Isoform Selectivity

Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

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