scholarly journals SsPEP1, an Effector with Essential Cellular Functions in Sugarcane Smut Fungus

2021 ◽  
Vol 7 (11) ◽  
pp. 954
Author(s):  
Shan Lu ◽  
Yukun Wang ◽  
Xiaorui Shen ◽  
Feng Guo ◽  
Chunling Zhou ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Mapk Signaling ◽  
Symptom Development ◽  
Cellular Functions ◽  
Sporisorium Scitamineum ◽  
Expression Of Genes ◽  
Allele Dosage ◽  
Biotrophic Fungi ◽  
Related Stress ◽  
Important Disease

Biotrophic fungi have to infect their host to obtain nutrients and must establish an interaction with the host to complete their life cycle. In this process, effectors play important roles in manipulating the host’s immune system to avoid being attacked. Sporisorium scitamineum is the causative agent of sugarcane smut, the most important disease in sugarcane-producing regions worldwide. In this work, we functionally characterized the conserved effector PEP1 in S. scitamineum. The mating process and the expression of genes in the MAPK signaling pathway and the a and b loci were adversely affected in Sspep1-null mutants. The requirement for SsPEP1 in pathogenicity and symptom development was allele dosage-dependent, i.e., deleting one Sspep1 allele in the mating pair turned a normal black whip with abundant teliospores into a white whip with few teliospores; however, deleting both alleles almost abolished infectivity and whip development. ΔSspep1 mutants produced significantly less mycelium mass within infected plants. Additionally, SsPEP1 was identified as a potent inhibitor of sugarcane POD-1a peroxidase activity, implying that SsPEP1 may function to relieve reactive oxygen species-related stress within the host plant. Taken together, our work demonstrated that SsPEP1 is a multifaceted effector essential for S. scitamineum growth, development, and pathogenicity.

scholarly journals Preconditioning by Hydrogen Peroxide Enhances Multiple Properties of HumanDecidua BasalisMesenchymal Stem/Multipotent Stromal Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
T. Khatlani ◽  
D. Algudiri ◽  
R. Alenzi ◽  
A. M. Al Subayyil ◽  
F. M. Abomaray ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Stem Cell ◽  
Cellular Functions ◽  
Beneficial Effects ◽  
Decidua Basalis ◽  
Expression Of Genes ◽  
Toxic Environment ◽  
Stress Environment ◽  
And Migration ◽  
Hostile Environments

Stem cell-based therapies rely on stem cell ability to repair in an oxidative stress environment. Preconditioning of mesenchymal stem cells (MSCs) to a stress environment has beneficial effects on their ability to repair injured tissues. We previously reported that MSCs from thedecidua basalis(DBMSCs) of human placenta have many important cellular functions that make them potentially useful for cell-based therapies. Here, we studied the effect of DBMSC preconditioning to a stress environment. DBMSCs were exposed to various concentrations of hydrogen peroxide (H2O2), and their functions were then assessed. DBMSC expression of immune molecules after preconditioning was also determined. DBMSC preconditioning with H2O2enhanced their proliferation, colonogenicity, adhesion, and migration. In addition, DBMSCs regardless of H2O2treatment displayed antiangiogenic activity. H2O2preconditioning also increased DBMSC expression of genes that promote cellular functions and decreased the expression of genes, which have opposite effect on their functions. Preconditioning also reduced DBMSC expression of IL-1β, but had no effects on the expression of other immune molecules that promote proliferation, adhesion, and migration. These data show that DBMSCs resist a toxic environment, which adds to their potential as a candidate stem cell type for treating various diseases in hostile environments.

scholarly journals Ent-Peniciherqueinone Suppresses Acetaldehyde-Induced Cytotoxicity and Oxidative Stress by Inducing ALDH and Suppressing MAPK Signaling

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1229
Author(s):  
Taehoon Oh ◽  
Mincheol Kwon ◽  
Jae Sik Yu ◽  
Mina Jang ◽  
Gun-Hee Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Modern Society ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
Ros Scavenging ◽  
Protein Levels ◽  
Cellular Reactive Oxygen Species ◽  
Related Stress ◽  
And Oxidative Stress

Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, ent-peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells. In addition, EPQ reduced cellular reactive oxygen species (ROS) levels and restored acetaldehyde-mediated disruption of mitochondrial membrane potential. Western blot analyses revealed that EPQ treatment increased protein levels of ROS-scavenging heme oxygenase-1 and superoxide dismutase, as well as the levels of aldehyde dehydrogenase (ALDH) 1, ALDH2, and ALDH3, under acetaldehyde-induced cellular stress. Finally, EPQ reduced acetaldehyde-induced phosphorylation of p38 and c-Jun N-terminal kinase, which are associated with ROS-induced oxidative stress. Therefore, our results demonstrated that EPQ prevents cellular oxidative stress caused by acetaldehyde and functions as a potent agent to suppress hangover symptoms and alcohol-related stress.

scholarly journals In the Model Host Caenorhabditis elegans, Sphingosine-1-Phosphate-Mediated Signaling Increases Immunity toward Human Opportunistic Bacteria

2020 ◽  
Vol 21 (21) ◽  
pp. 7813
Author(s):  
Kiho Lee ◽  
Iliana Escobar ◽  
Yeeun Jang ◽  
Wooseong Kim ◽  
Frederick M. Ausubel ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Responses ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Kinase Gene ◽  
Concentration Dependent Manner ◽  
C Elegans ◽  
Opportunistic Bacteria ◽  
Free Living Nematode

Sphingosine-1-phophate (S1P) is a sphingolipid-derived signaling molecule that controls diverse cellular functions including cell growth, homeostasis, and stress responses. In a variety of metazoans, cytosolic S1P is transported into the extracellular space where it activates S1P receptors in a concentration-dependent manner. In the free-living nematode Caenorhabditis elegans, the spin-2 gene, which encodes a S1P transporter, is activated during Gram-positive or Gram-negative bacterial infection of the intestine. However, the role during infection of spin-2 and three additional genes in the C. elegans genome encoding other putative S1P transporters has not been elucidated. Here, we report an evolutionally conserved function for S1P and a non-canonical role for S1P transporters in the C. elegans immune response to bacterial pathogens. We found that mutations in the sphingosine kinase gene (sphk-1) or in the S1P transporter genes spin-2 or spin-3 decreased nematode survival after infection with Pseudomonas aeruginosa or Enterococcus faecalis. In contrast to spin-2 and spin-3, mutating spin-1 leads to an increase in resistance to P. aeruginosa. Consistent with these results, when wild-type C. elegans were supplemented with extracellular S1P, we found an increase in their lifespan when challenged with P. aeruginosa and E. faecalis. In comparison, spin-2 and spin-3 mutations suppressed the ability of S1P to rescue the worms from pathogen-mediated killing, whereas the spin-1 mutation had no effect on the immune-enhancing activity of S1P. S1P demonstrated no antimicrobial activity toward P. aeruginosa and Escherichia coli and only minimal activity against E. faecalis MMH594 (40 µM). These data suggest that spin-2 and spin-3, on the one hand, and spin-1, on the other hand, transport S1P across cellular membranes in opposite directions. Finally, the immune modulatory effect of S1P was diminished in C. eleganssek-1 and pmk-1 mutants, suggesting that the immunomodulatory effects of S1P are mediated by the p38 MAPK signaling pathway.

scholarly journals Resistance Mechanisms of Saccharomyces cerevisiae to Commercial Formulations of Glyphosate Involve DNA Damage Repair, the Cell Cycle, and the Cell Wall Structure

2020 ◽  
Vol 10 (6) ◽  
pp. 2043-2056
Author(s):  
Apoorva Ravishankar ◽  
Amaury Pupo ◽  
Jennifer E. G. Gallagher
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Resistance Mechanisms ◽  
Mapk Signaling ◽  
Fragile Sites ◽  
Cell Wall Structure ◽  
Wall Structure ◽  
Global Changes ◽  
Expression Of Genes ◽  
Wide Range

The use of glyphosate-based herbicides is widespread and despite their extensive use, their effects are yet to be deciphered completely. The additives in commercial formulations of glyphosate, though labeled inert when used individually, have adverse effects when used in combination with other additives along with the active ingredient. As a species, Saccharomyces cerevisiae has a wide range of resistance to glyphosate-based herbicides. To investigate the underlying genetic differences between sensitive and resistant strains, global changes in gene expression were measured, when yeast were exposed to a glyphosate-based herbicide (GBH). Expression of genes involved in numerous pathways crucial to the cell’s functioning, such as DNA replication, MAPK signaling, meiosis, and cell wall synthesis changed. Because so many diverse pathways were affected, these strains were then subjected to in-lab-evolutions (ILE) to select mutations that confer increased resistance. Common fragile sites were found to play a role in adaptation to resistance to long-term exposure of GBHs. Copy number increased in approximately 100 genes associated with cell wall proteins, mitochondria, and sterol transport. Taking ILE and transcriptomic data into account it is evident that GBHs affect multiple biological processes in the cell. One such component is the cell wall structure which acts as a protective barrier in alleviating the stress caused by exposure to inert additives in GBHs. Sed1, a GPI-cell wall protein, plays an important role in tolerance of a GBH. Hence, a detailed study of the changes occurring at the genome and transcriptome levels is essential to better understand the effects of an environmental stressor such as a GBH, on the cell as a whole.

scholarly journals Identification of a novel selective and potent inhibitor of glycogen synthase kinase-3

2019 ◽  
Vol 317 (6) ◽  
pp. C1289-C1303 ◽  
Author(s):  
Mahboubeh S. Noori ◽  
Pooja M. Bhatt ◽  
Maria C. Courreges ◽  
Davoud Ghazanfari ◽  
Chaz Cuckler ◽  
...  
Keyword(s):  
Design Space ◽  
Potent Inhibitor ◽  
Glycogen Synthase ◽  
Selective Inhibition ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cellular Functions ◽  
Starting Point ◽  
Potential Therapeutics

Glycogen synthase kinase-3 (GSK-3) is a multitasking protein kinase that regulates numerous critical cellular functions. Not surprisingly, elevated GSK-3 activity has been implicated in a host of diseases including pathological inflammation, diabetes, cancer, arthritis, asthma, bipolar disorder, and Alzheimer’s. Therefore, reagents that inhibit GSK-3 activity provide a means to investigate the role of GSK-3 in cellular physiology and pathophysiology and could become valuable therapeutics. Finding a potent inhibitor of GSK-3 that can selectively target this kinase, among over 500 protein kinases in the human genome, is a significant challenge. Thus there remains a critical need for the identification of selective inhibitors of GSK-3. In this work, we introduce a novel small organic compound, namely COB-187, which exhibits potent and highly selective inhibition of GSK-3. Specifically, this study 1) utilized a molecular screen of 414 kinase assays, representing 404 unique kinases, to reveal that COB-187 is a highly potent and selective inhibitor of GSK-3; 2) utilized a cellular assay to reveal that COB-187 decreases the phosphorylation of canonical GSK-3 substrates indicating that COB-187 inhibits cellular GSK-3 activity; and 3) reveals that a close isomer of COB-187 is also a selective and potent inhibitor of GSK-3. Taken together, these results demonstrate that we have discovered a region of chemical design space that contains novel GSK-3 inhibitors. These inhibitors will help to elucidate the intricate function of GSK-3 and can serve as a starting point for the development of potential therapeutics for diseases that involve aberrant GSK-3 activity.

scholarly journals Effects of Low-Shear Modeled Microgravity on Cell Function, Gene Expression, and Phenotype in Saccharomyces cerevisiae

2006 ◽  
Vol 72 (7) ◽  
pp. 4569-4575 ◽  
Author(s):  
B. Purevdorj-Gage ◽  
K. B. Sheehan ◽  
L. E. Hyman
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Cell Function ◽  
Yeast Cells ◽  
Lag Phase ◽  
Limited Information ◽  
Cellular Functions ◽  
Modeled Microgravity ◽  
Expression Of Genes ◽  
Low Shear

ABSTRACT Only limited information is available concerning the effects of low-shear modeled microgravity (LSMMG) on cell function and morphology. We examined the behavior of Saccharomyces cerevisiae grown in a high-aspect-ratio vessel, which simulates the low-shear and microgravity conditions encountered in spaceflight. With the exception of a shortened lag phase (90 min less than controls; P < 0.05), yeast cells grown under LSMMG conditions did not differ in growth rate, size, shape, or viability from the controls but did differ in the establishment of polarity as exhibited by aberrant (random) budding compared to the usual bipolar pattern of controls. The aberrant budding was accompanied by an increased tendency of cells to clump, as indicated by aggregates containing five or more cells. We also found significant changes (greater than or equal to twofold) in the expression of genes associated with the establishment of polarity (BUD5), bipolar budding (RAX1, RAX2, and BUD25), and cell separation (DSE1, DSE2, and EGT2). Thus, low-shear environments may significantly alter yeast gene expression and phenotype as well as evolutionary conserved cellular functions such as polarization. The results provide a paradigm for understanding polarity-dependent cell responses to microgravity ranging from pathogenesis in fungi to the immune response in mammals.

scholarly journals Orostachys japonicusInhibits Expression of the TLR4, NOD2, iNOS, and COX-2 Genes in LPS-Stimulated Human PMA-Differentiated THP-1 Cells by Inhibiting NF-κB and MAPK Activation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yeo-Kwang Yoon ◽  
Hong-Jung Woo ◽  
Youngchul Kim
Keyword(s):  
Mapk Signaling ◽  
Mrna Levels ◽  
Inflammatory Agent ◽  
Expression Of Genes ◽  
Erk Phosphorylation ◽  
Genes Encoding ◽  
Pathogen Recognition Receptors ◽  
Cox 2 ◽  
High Concentrations ◽  
Proinflammatory Factors

Orostachys japonicusis traditionally used as an inflammatory agent. In this report, we investigated the effects ofO. japonicusextract on the expression of genes encoding pathogen-recognition receptors (TLR2, TLR4, NOD1, and NOD2) and proinflammatory factors (iNOS, COX-2, and cytokines) in LPS-stimulated PMA-differentiated THP-1 cells and the NF-κB and MAPK pathways.O. japonicusinduced toxicity at high concentrations but had no effect at concentrations lower than 25 μg/mL.O. japonicusinhibited LPS-induced TLR4 and NOD2 mRNA levels, suppressed LPS-induced iNOS and COX-2 transcription and translocation, and downregulated LPS-induced proinflammatory cytokine (IL-1β, IL-6, IL-8, and TNF-α) mRNA levels. In addition,O. japonicusinhibited LPS-induced NF-κB activation and IκBαdegradation and suppressed LPS-induced JNK, p38 MAPK, and ERK phosphorylation. Overall, our results demonstrate that the anti-inflammatory effects ofO. japonicusare mediated by suppression of NF-κB and MAPK signaling, resulting in reduced TLR4, NOD2, iNOS, and COX-2 expression and inhibition of inflammatory cytokine expression.

scholarly journals Comparison of Host Gene Expression Profiles in Spleen Tissues of Genetically Susceptible and Resistant Mice during ECTV Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Wen-Yu Cheng ◽  
Huai-Jie Jia ◽  
Xiao-Bing He ◽  
Guo-Hua Chen ◽  
Yuan Feng ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mapk Signaling ◽  
Mouse Strains ◽  
Resistant Mouse ◽  
Gene Profiles ◽  
Expression Of Genes ◽  
Leukocyte Transendothelial Migration ◽  
Specific Virus

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirusrelationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirusinteraction.

scholarly journals Frequency of MicroRNA Response Elements Identifies Pathologically Relevant Signaling Pathways in Cancers

2019 ◽  
Author(s):  
Asha A. Nair ◽  
Xiaojia Tang ◽  
Kevin J. Thompson ◽  
Krishna R. Kalari ◽  
Subbaya Subramanian
Keyword(s):  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Breast Cancers ◽  
Cellular Functions ◽  
Protein Coding ◽  
Interacting Protein ◽  
Response Elements ◽  
Normal Tissues ◽  
Complex Interactions ◽  
Cancer Tumor

ABSTRACTComplex interactions between mRNAs and microRNAs influence cellular functions. The interactions between mRNA and microRNAs also determine the post-transcriptional availability of free mRNAs and unbound microRNAs. The microRNAs bind to one or more microRNA Response Elements (MREs) predominantly located on the 3’untranslated regions (3’UTR) of mRNAs. In this study, we leveraged MRE sites and their frequencies in transcriptomes of cancer and matched normal tissues to obtain insights into disease-specific interactions between mRNAs and microRNAs. Toward this, we developed a novel bioinformatics method called ‘ReMIx’ that utilizes RNA-Seq data to quantify MRE frequencies at 3’UTR of genes across the transcriptome. We applied ReMIx to The Cancer Genome Atlas (TCGA) Triple Negative (TN) breast cancer tumor-normal adjacent pairs (N=13) and identified distinctly and differentially expressed MREs specific to the TN tumors. Novel data generated by ReMIx identified candidate mRNAs and microRNAs in the MAPK signaling cascade of the TN tumors. We further analyzed the MAPK endogenous RNA network to establish regulatory microRNA partners, along with interacting protein-coding mRNAs that influence and modulate MAPK signaling in TN breast cancers.

scholarly journals The neocortical progenitor specification program is established through combined modulation of SHH and FGF signaling

2019 ◽  
Author(s):  
Odessa R. Yabut ◽  
Hui-Xuan Ng ◽  
Keejung Yoon ◽  
Jessica C. Arela ◽  
Thomas Ngo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Fgf Signaling ◽  
Shh Signaling ◽  
Neuronal Progenitors ◽  
Downstream Effector ◽  
Expression Of Genes ◽  
Show Evidence ◽  
Ectopic Activation ◽  
Low Levels

ABSTRACTNeuronal progenitors in the developing forebrain undergo dynamic competence states to ensure timely generation of specific excitatory and inhibitory neuronal subtypes from distinct neurogenic niches of the dorsal and ventral forebrain, respectively. Here we show evidence of progenitor plasticity when Sonic hedgehog (SHH) signaling is left unmodulated in the embryonic neocortex of the dorsal forebrain. At early stages of corticogenesis, loss of Suppressor of Fused (Sufu), a potent inhibitor of SHH signaling, in neocortical progenitors, altered their transcriptomic landscape. Ectopic activation of SHH signaling occurred, via degradation of Gli3R, resulting in significant upregulation of Fibroblast Growth Factor 15 (FGF15) gene expression. Consequently, activation of FGF signaling, and its downstream effector the MAPK signaling, facilitated expression of genes characteristic of ventral forebrain progenitors. Our studies identify the importance of modulating extrinsic niche signals such as SHH and FGF15 to maintain the competency and specification program of neocortical progenitors throughout corticogenesis.SIGNIFICANCE STATEMENTLow levels of FGF15 control progenitor proliferation and differentiation during neocortical development but little is known on how FGF15 expression is maintained. Our studies identified SHH signaling as a critical activator of FGF15 expression during corticogenesis. We found that Sufu, via Gli3R, ensured low levels of FGF15 was expressed to prevent abnormal specification of neocortical progenitors. These studies advance our knowledge on the molecular mechanisms guiding the generation of specific neocortical neuronal lineages, their implications in neurodevelopmental diseases, and may guide future studies on how progenitor cells may be utilized for brain repair.

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