scholarly journals ADP-ribosylation signalling and human disease

Open Biology ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 190041 ◽  
Author(s):  
Luca Palazzo ◽  
Petra Mikolčević ◽  
Andreja Mikoč ◽  
Ivan Ahel
Keyword(s):  
Neurological Disorders ◽  
Fine Tuning ◽  
Molecular Medicine ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Damage Repair ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
The Impact

ADP-ribosylation (ADPr) is a reversible post-translational modification of proteins, which controls major cellular and biological processes, including DNA damage repair, cell proliferation and differentiation, metabolism, stress and immune responses. In order to maintain the cellular homeostasis, diverse ADP-ribosyl transferases and hydrolases are involved in the fine-tuning of ADPr systems. The control of ADPr network is vital, and dysregulation of enzymes involved in the regulation of ADPr signalling has been linked to a number of inherited and acquired human diseases, such as several neurological disorders and in cancer. Conversely, the therapeutic manipulation of ADPr has been shown to ameliorate several disorders in both human and animal models. These include cardiovascular, inflammatory, autoimmune and neurological disorders. Herein, we summarize the recent findings in the field of ADPr, which support the impact of this modification in human pathophysiology and highlight the curative potential of targeting ADPr for translational and molecular medicine.

scholarly journals Human microRNAs in host–parasite interaction: a review

3 Biotech ◽  
2020 ◽  
Vol 10 (12) ◽  
Author(s):  
Sujay Paul ◽  
Luis M. Ruiz-Manriquez ◽  
Francisco I. Serrano-Cano ◽  
Carolina Estrada-Meza ◽  
Karla A. Solorio-Diaz ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Fine Tuning ◽  
Transcriptional Level ◽  
Response Modulation ◽  
Rna Molecules ◽  
Small Noncoding Rna ◽  
Diagnosis And Prognosis ◽  
Cell Proliferation And Differentiation ◽  
Host Parasite ◽  
The Impact

AbstractMicroRNAs (miRNAs) are a group of small noncoding RNA molecules with significant capacity to regulate the gene expression at the post-transcriptional level in a sequence-specific manner either through translation repression or mRNA degradation triggering a fine-tuning biological impact. They have been implicated in several processes, including cell growth and development, signal transduction, cell proliferation and differentiation, metabolism, apoptosis, inflammation, and immune response modulation. However, over the last few years, extensive studies have shown the relevance of miRNAs in human pathophysiology. Common human parasitic diseases, such as Malaria, Leishmaniasis, Amoebiasis, Chagas disease, Schistosomiasis, Toxoplasmosis, Cryptosporidiosis, Clonorchiasis, and Echinococcosis are the leading cause of death worldwide. Thus, identifying and characterizing parasite-specific miRNAs and their host targets, as well as host-related miRNAs, are important for a deeper understanding of the pathophysiology of parasite-specific diseases at the molecular level. In this review, we have demonstrated the impact of human microRNAs during host−parasite interaction as well as their potential to be used for diagnosis and prognosis purposes.

scholarly journals Bisphenol A alters differentiation of Leydig cells in the rabbit fetal testis

2020 ◽  
Vol 52 ◽  
Author(s):  
Alexis Paulina Ortega-García ◽  
Verónica Díaz-Hernández ◽  
Pedro Collazo-Saldaña ◽  
Horacio Merchant-Larios
Keyword(s):  
Bisphenol A ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Disruptive Effect ◽  
Paracrine Signaling ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Tissue Compartments ◽  
Fetal Organs ◽  
The Impact

The endocrine disruptor Bisphenol A (BPA) crosses the placental barrier and reaches the fetal organs, including the gonads. In the testis, fetal Leydig cells (FLC) produce testosterone required for the male phenotype and homeostatic cell-cell signaling in the developing testis. Although it is known that BPA affects cell proliferation and differentiation in FLC, results concerning the mechanism involved are contradictory, mainly due to differences among species. Fast developing fetal gonads of rodents lack cortex and medulla, whereas species with more extended gestation periods form these two tissue compartments. The rabbit provides a good subject for studying the disruptive effect of BPA in fetal Leydig and possible postnatal endocrine consequences in adult Leydig cells. Here, we investigated the impact of BPA administered to pregnant rabbits does, on the FLC population of the developing testes. Using qRT-PCR, we assessed the levels of SF1, CYP11A1, 3β-HSD, and androgen receptor (AR) genes, and levels of fetal serum testosterone were measured by ELISA. These levels correlated with both the mitotic activity and the ultrastructural differentiation of the FLC by confocal and electron microscopy, respectively. Results indicate that BPA alters the expression levels of essential genes involved in androgen paracrine signaling, modifies the proliferation and differentiation of the FLCs, and alters the levels of serum testosterone after birth. Thus, BPA may change the postnatal levels of serum testosterone due to the impaired FLC population formed by the proliferating stem and non-proliferating cytodifferentiated FLC.

scholarly journals Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shinichiro Hayashi ◽  
Ichiro Manabe ◽  
Yumi Suzuki ◽  
Frédéric Relaix ◽  
Yumiko Oishi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Biological Processes ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Acting In Concert

Krüppel-like factor 5 (Klf5) is a zinc-finger transcription factor that controls various biological processes, including cell proliferation and differentiation. We show that Klf5 is also an essential mediator of skeletal muscle regeneration and myogenic differentiation. During muscle regeneration after injury (cardiotoxin injection), Klf5 was induced in the nuclei of differentiating myoblasts and newly formed myofibers expressing myogenin in vivo. Satellite cell-specific Klf5 deletion severely impaired muscle regeneration, and myotube formation was suppressed in Klf5-deleted cultured C2C12 myoblasts and satellite cells. Klf5 knockdown suppressed induction of muscle differentiation-related genes, including myogenin. Klf5 ChIP-seq revealed that Klf5 binding overlaps that of MyoD and Mef2, and Klf5 physically associates with both MyoD and Mef2. In addition, MyoD recruitment was greatly reduced in the absence of Klf5. These results indicate that Klf5 is an essential regulator of skeletal muscle differentiation, acting in concert with myogenic transcription factors such as MyoD and Mef2.

scholarly journals The Antioxidant Phytochemical Schisandrin A Promotes Neural Cell Proliferation and Differentiation after Ischemic Brain Injury

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7466
Author(s):  
Wentian Zong ◽  
Mostafa Gouda ◽  
Enli Cai ◽  
Ruofeng Wang ◽  
Weijie Xu ◽  
...  
Keyword(s):  
Neural Progenitor Cell ◽  
Nerve Fibers ◽  
Specific Class ◽  
Class Iii ◽  
Promoting Effect ◽  
Western Blot Assay ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Late Recovery ◽  
The Impact

Schisandrin A (SCH) is a natural bioactive phytonutrient that belongs to the lignan derivatives found in Schisandra chinensis fruit. This study aims to investigate the impact of SCH on promoting neural progenitor cell (NPC) regeneration for avoiding stroke ischemic injury. The promoting effect of SCH on NPCs was evaluated by photothrombotic model, immunofluorescence, cell line culture of NPCs, and Western blot assay. The results showed that neuron-specific class III beta-tubulin (Tuj1) was positive with Map2 positive nerve fibers in the ischemic area after using SCH. In addition, Nestin and SOX2 positive NPCs were significantly (p < 0.05) increased in the penumbra and core. Further analysis identified that SCH can regulate the expression level of cell division control protein 42 (Cdc42). In conclusion, our findings suggest that SCH enhanced NPCs proliferation and differentiation possible by Cdc42 to regulated cytoskeletal rearrangement and polarization of cells, which provides new hope for the late recovery of stroke.

scholarly journals Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy

2019 ◽  
Author(s):  
Alessia Galasso ◽  
Daria Iakovleva ◽  
Luis Alberto Baena-Lopez
Keyword(s):  
Stem Cell ◽  
Fine Tuning ◽  
Caspase Activation ◽  
Cellular Functions ◽  
Hedgehog Signalling ◽  
Cell Functions ◽  
Metabolic Defects ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Moderate Stress

ABSTRACTThere is increasing evidence associating the activity of caspases with the regulation of basic cellular functions beyond apoptosis. Accordingly, the dysregulation of these novel non-apoptotic functions often sits at the origin of neurological disorders, metabolic defects, autoimmunity, and cancer. However, the molecular interplay between caspases and the signalling networks active in non-apoptotic cellular scenarios remains largely unknown. Our work show that non-apoptotic caspase activation is critical to modulate Hedgehog-signalling and autophagy in ovarian somatic cells from both Drosophila and humans under moderate stress. We also demonstrate that these novel caspase functions are key to sustain stem cell proliferation and differentiation without inducing apoptosis. Finally, we molecularly link these caspase-dependent effects to the fine-tuning of the Hedgehog-receptor, Patched. Together, these findings confer a pro-survival role to the caspases, as opposed to the widely held apoptotic function assigned to these enzymes.

scholarly journals Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin remodeling

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jugal Mohapatra ◽  
Kyuto Tashiro ◽  
Ryan L Beckner ◽  
Jorge Sierra ◽  
Jessica A Kilgore ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Protein Function ◽  
Post Translational Modification ◽  
Site Specific ◽  
Precise Control ◽  
Protein Ligation ◽  
Adp Ribosylation ◽  
Nuclear Extracts ◽  
Synthesis Strategy ◽  
The Impact

Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. As the list of PARP1/2:HPF1 substrates continues to expand, there is a need for technologies to prepare mono- and poly-ADP-ribosylated proteins for biochemical interrogation. Here we investigate the unique peptide ADPr activities catalyzed by PARP1 in the absence and presence of HPF1. We then exploit these activities to develop a method that facilitates installation of ADP-ribose polymers onto peptides with precise control over chain length and modification site. Importantly, the enzymatically mono- and poly-ADP-ribosylated peptides are fully compatible with protein ligation technologies. This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at H2BS6 or H3S10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. We found ALC1 preferentially remodels 'activated' substrates within heterogeneous mononucleosome populations and asymmetrically ADP-ribosylated dinucleosome substrates, and that nucleosome serine ADPr is sufficient to stimulate ALC1 activity in nuclear extracts. Our study identifies a biochemical function for nucleosome serine ADPr and describes a new, highly modular approach to explore the impact that site-specific serine mono- and poly-ADPr have on protein function.

scholarly journals Consequences of early postnatal lipopolysaccharide exposure on developing lungs in mice

2019 ◽  
Vol 316 (1) ◽  
pp. L229-L244 ◽  
Author(s):  
Amrit Kumar Shrestha ◽  
Matthew L. Bettini ◽  
Renuka T. Menon ◽  
Vashisht Y. N. Gopal ◽  
Shixia Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Development ◽  
Dependent Manner ◽  
T Regulatory Cell ◽  
Lung Macrophage ◽  
Flow Cytometric ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Apoptosis ◽  
Proliferation And Differentiation ◽  
The Impact

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infants that is characterized by interrupted lung development. Postnatal sepsis causes BPD, yet the contributory mechanisms are unclear. To address this gap, studies have used lipopolysaccharide (LPS) during the alveolar phase of lung development. However, the lungs of infants who develop BPD are still in the saccular phase of development, and the effects of LPS during this phase are poorly characterized. We hypothesized that chronic LPS exposure during the saccular phase disrupts lung development by mechanisms that promote inflammation and prevent optimal lung development and repair. Wild-type C57BL6J mice were intraperitoneally administered 3, 6, or 10 mg/kg of LPS or a vehicle once daily on postnatal days (PNDs) 3–5. The lungs were collected for proteomic and genomic analyses and flow cytometric detection on PND6. The impact of LPS on lung development, cell proliferation, and apoptosis was determined on PND7. Finally, we determined differences in the LPS effects between the saccular and alveolar lungs. LPS decreased the survival and growth rate and lung development in a dose-dependent manner. These effects were associated with a decreased expression of proteins regulating cell proliferation and differentiation and increased expression of those mediating inflammation. While the lung macrophage population of LPS-treated mice increased, the T-regulatory cell population decreased. Furthermore, LPS-induced inflammatory and apoptotic response and interruption of cell proliferation and alveolarization was greater in alveolar than in saccular lungs. Collectively, the data support our hypothesis and reveal several potential therapeutic targets for sepsis-mediated BPD in infants.

scholarly journals The Impact of the Ca2+-Independent Phospholipase A2β (iPLA2β) on Immune Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 577
Author(s):  
Tayleur D. White ◽  
Abdulaziz Almutairi ◽  
Ying Gai Tusing ◽  
Xiaoyong Lei ◽  
Sasanka Ramanadham
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Immune Cells ◽  
Neurological Disorders ◽  
Male Fertility ◽  
Metabolic Disorders ◽  
Potential Contribution ◽  
Biological Processes ◽  
Membrane Remodeling ◽  
The Impact

The Ca2+-independent phospholipase A2β (iPLA2β) is a member of the PLA2 family that has been proposed to have roles in multiple biological processes including membrane remodeling, cell proliferation, bone formation, male fertility, cell death, and signaling. Such involvement has led to the identification of iPLA2β activation in several diseases such as cancer, cardiovascular abnormalities, glaucoma, periodontitis, neurological disorders, diabetes, and other metabolic disorders. More recently, there has been heightened interest in the role that iPLA2β plays in promoting inflammation. Recognizing the potential contribution of iPLA2β in the development of autoimmune diseases, we review this issue in the context of an iPLA2β link with macrophages and T-cells.

Molecular context of ADP-ribosylation in schistosomes for drug discovery and vaccine development

2020 ◽  
Vol 17 ◽  
Author(s):  
Amandla Chutshela ◽  
Priscilla Masamba ◽  
Babatunji Emmanuel Oyinloye ◽  
Abidemi Paul Kappo
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Vaccine Development ◽  
Neglected Tropical Diseases ◽  
Adenosine Diphosphate ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Molecular Context ◽  
Living Organisms

: Schistosome infection is regarded as one of the most important and neglected tropical diseases associated with poor sanitation. Like other living organisms, schistosomes employ multiple biological processes, of which some are regulated by a post-translational modification called Adenosine diphosphate-ribosylation (ADP-ribosylation), catalyzed by ADPribosyltransferases. ADP-ribosylation is the addition of ADP-ribose moieties from nicotinamide adenine dinucleotide (NAD+) to various targets, which include proteins and nucleotides. It is crucial in biological processes such as DNA repair, apoptosis, carbohydrate metabolism and catabolism. In the absence of a vaccine against schistosomiasis, this becomes a promising pathway in the identification of drug targets against various forms of this infection. The tegument of the worm is an encouraging immunogenic target for anti-schistosomal vaccine development. Vaccinology, molecular modeling and target-based drug discovery strategies have been used for years in drug discovery and for vaccine development. In this paper, we outline ADP-ribosylation and other different approaches to drug discovery and vaccine development against schistosomiasis.

scholarly journals The Impact of Metallic Nanoparticles on Stem Cell Proliferation and Differentiation

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 761 ◽  
Author(s):  
Ahmed Abdal Dayem ◽  
Soo Lee ◽  
Ssang-Goo Cho
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Metallic Nanoparticles ◽  
Stem Cell Differentiation ◽  
Stem Cell Proliferation ◽  
Cell Functions ◽  
Cell Proliferation And Differentiation ◽  
Wide Range ◽  
Proliferation And Differentiation ◽  
The Impact

Nanotechnology has a wide range of medical and industrial applications. The impact of metallic nanoparticles (NPs) on the proliferation and differentiation of normal, cancer, and stem cells is well-studied. The preparation of NPs, along with their physicochemical properties, is related to their biological function. Interestingly, various mechanisms are implicated in metallic NP-induced cellular proliferation and differentiation, such as modulation of signaling pathways, generation of reactive oxygen species, and regulation of various transcription factors. In this review, we will shed light on the biomedical application of metallic NPs and the interaction between NPs and the cellular components. The in vitro and in vivo influence of metallic NPs on stem cell differentiation and proliferation, as well as the mechanisms behind potential toxicity, will be explored. A better understanding of the limitations related to the application of metallic NPs on stem cell proliferation and differentiation will afford clues for optimal design and preparation of metallic NPs for the modulation of stem cell functions and for clinical application in regenerative medicine.

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