scholarly journals Role of APD-Ribosylation in Bone Health and Disease

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1201 ◽  
Author(s):  
Wang ◽  
Mbalaviele
Keyword(s):  
Bone Development ◽  
Adenosine Diphosphate ◽  
Signaling Networks ◽  
Post Translational Modification ◽  
Cell Behaviors ◽  
Adp Ribosylation ◽  
Protein Functions ◽  
Health And Disease ◽  
Underlying Mechanisms

The transfer of adenosine diphosphate (ADP)-ribose unit(s) from nicotinamide adenine dinucleotide (NAD+) to acceptor proteins is known as ADP-ribosylation. This post-translational modification (PTM) unavoidably alters protein functions and signaling networks, thereby impacting cell behaviors and tissue outcomes. As a ubiquitous mechanism, ADP-ribosylation affects multiple tissues, including bones, as abnormal ADP-ribosylation compromises bone development and remodeling. In this review, we describe the effects of ADP-ribosylation in bone development and maintenance, and highlight the underlying mechanisms.

scholarly journals The Critical Role of PARPs in Regulating Innate Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Huifang Zhu ◽  
Yan-Dong Tang ◽  
Guoqing Zhan ◽  
Chenhe Su ◽  
Chunfu Zheng
Keyword(s):  
Immune Responses ◽  
Critical Role ◽  
Molecular Targets ◽  
Adenosine Diphosphate ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Adp Ribosylation

Poly (adenosine diphosphate-ribose) polymerases (PARPs) are a family of proteins responsible for transferring ADP-ribose groups to target proteins to initiate the ADP-ribosylation, a highly conserved and fundamental post-translational modification in all organisms. PARPs play important roles in various cellular functions, including regulating chromatin structure, transcription, replication, recombination, and DNA repair. Several studies have recently converged on the widespread involvement of PARPs and ADP-Ribosylation reaction in mammalian innate immunity. Here, we provide an overview of the emerging roles of PARPs family and ADP-ribosylation in regulating the host’s innate immune responses involved in cancers, pathogenic infections, and inflammations, which will help discover and design new molecular targets for cancers, pathogenic infections, and inflammations.

ADP-ribosylation and intracellular traffic: an emerging role for PARP enzymes

2019 ◽  
Vol 47 (1) ◽  
pp. 357-370 ◽  
Author(s):  
Giovanna Grimaldi ◽  
Daniela Corda
Keyword(s):  
Intracellular Transport ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Intracellular Traffic ◽  
Adp Ribosylation ◽  
Cell Responses ◽  
Physiological Processes ◽  
Dependent Cell ◽  
Ribose Moiety

AbstractADP-ribosylation is an ancient and reversible post-translational modification (PTM) of proteins, in which the ADP-ribose moiety is transferred from NAD+ to target proteins by members of poly-ADP-ribosyl polymerase (PARP) family. The 17 members of this family have been involved in a variety of cellular functions, where their regulatory roles are exerted through the modification of specific substrates, whose identification is crucial to fully define the contribution of this PTM. Evidence of the role of the PARPs is now available both in the context of physiological processes and of cell responses to stress or starvation. An emerging role of the PARPs is their control of intracellular transport, as it is the case for tankyrases/PARP5 and PARP12. Here, we discuss the evidence pointing at this novel aspect of PARPs-dependent cell regulation.

scholarly journals In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Angelica Aguilera-Gomez ◽  
Marinke M van Oorschot ◽  
Tineke Veenendaal ◽  
Catherine Rabouille
Keyword(s):  
Amino Acid ◽  
Metabolic Stress ◽  
Amino Acid Starvation ◽  
Critical Event ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Body Component ◽  
Necessary And Sufficient

PARP catalysed ADP-ribosylation is a post-translational modification involved in several physiological and pathological processes, including cellular stress. In order to visualise both Poly-, and Mono-, ADP-ribosylation in vivo, we engineered specific fluorescent probes. Using them, we show that amino-acid starvation triggers an unprecedented display of mono-ADP-ribosylation that governs the formation of Sec body, a recently identified stress assembly that forms in Drosophila cells. We show that dPARP16 catalytic activity is necessary and sufficient for both amino-acid starvation induced mono-ADP-ribosylation and subsequent Sec body formation and cell survival. Importantly, dPARP16 catalyses the modification of Sec16, a key Sec body component, and we show that it is a critical event for the formation of this stress assembly. Taken together our findings establish a novel example for the role of mono-ADP-ribosylation in the formation of stress assemblies, and link this modification to a metabolic stress.

scholarly journals Inhibitors of cholera toxin-induced adenosine diphosphate ribosylation of membrane-associated proteins block stem cell differentiation

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1544-1548 ◽  
Author(s):  
TM Dexter ◽  
AD Whetton ◽  
CM Heyworth
Keyword(s):  
Stem Cell Differentiation ◽  
Adenosine Diphosphate ◽  
Mature Cell ◽  
Adp Ribosylation ◽  
Colony Forming Units ◽  
Associated Proteins ◽  
Stimulating Factor ◽  
Cell Conditioned Medium

Abstract Two potent inhibitors of mono-adenosine diphosphate (ADP) ribosylation have recently been described and characterized, named p- methoxylbenzylaminodecamethylene guanidine sulfate (MBAMG) and benzylaminododecylguanine hydrochloride (BADGH). We have used these agents to investigate the role of ADP ribosylation in hematopoiesis using long-term marrow cultures. The addition of MBAMG (10(-6) mol/L) or BADGH (5 X 10(-4) mol/L) led to both an inhibition of mature cell production and the development of colony-stimulating factor (CSF-1)- responsive GM-CFC, but had no effect upon spleen colony-forming units (CFU-S) or on progenitor cells which respond to the multilineage stimulating factor present in WEHI-3B cell-conditioned medium. These data indicate that these inhibitors of mono-ADP ribosylation can block the commitment and/or differentiation of stem cells and infers that ADP ribosylation may be of some importance in the hematopoietic process.

scholarly journals Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 680
Author(s):  
Ann-Katrin Hopp ◽  
Michael O. Hottiger
Keyword(s):  
Nucleic Acids ◽  
Nicotinamide Adenine Dinucleotide ◽  
Physiological Function ◽  
Adenosine Diphosphate ◽  
Current Understanding ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
The Past ◽  
Technological Advances

Adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD+)-dependent post-translational modification that is found on proteins as well as on nucleic acids. While ARTD1/PARP1-mediated poly-ADP-ribosylation has extensively been studied in the past 60 years, comparably little is known about the physiological function of mono-ADP-ribosylation and the enzymes involved in its turnover. Promising technological advances have enabled the development of innovative tools to detect NAD+ and NAD+/NADH (H for hydrogen) ratios as well as ADP-ribosylation. These tools have significantly enhanced our current understanding of how intracellular NAD dynamics contribute to the regulation of ADP-ribosylation as well as to how mono-ADP-ribosylation integrates into various cellular processes. Here, we discuss the recent technological advances, as well as associated new biological findings and concepts.

scholarly journals Effects of Probiotics on Human Health and Disease: A Review

2021 ◽  
Vol 48 (1) ◽  
pp. 95-100
Author(s):  
A. Amiri ◽  
F. Firoozeh ◽  
M. Zibaei ◽  
A. Khaledi
Keyword(s):  
Human Health ◽  
Digestive System ◽  
Intestinal Microflora ◽  
Normal Flora ◽  
Beneficial Effects ◽  
Prevention And Treatment ◽  
Health And Disease ◽  
The Subject ◽  
Underlying Mechanisms

Abstract Alteration of the gut microbiome in order to achieve a balance in the normal flora of the intestine could be very beneficial in maintaining the health of the human. Probiotics are living microbial supplements that are added to the diet and have beneficial effects on the host by improving the balance of the intestinal microflora. The purpose of this study is to review previous studies on the effects of probiotics on human health and various diseases. The Farsi and English electronic databases such as, SID, Iranmedex, Magiran, Google Scholar, PubMed and ISI Web of Knowledge were searched and the published articles that have studied the effects of probiotics on the prevention and treatment of various diseases were included in the study. The review of published articles related to the subject showed that consumption of probiotics, prebiotics and proper diet have the significant effects on the health of the digestive system and has reduced and improved symptoms of different disorders and diseases. Further research is needed to better understand the underlying mechanisms of probiotic function and confirm the role of the probiotics in preventing and treating various types of cancers and other diseases.

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 AMPK: An Epigenetic Landscape Modulator

2018 ◽  
Vol 19 (10) ◽  
pp. 3238 ◽  
Author(s):  
Brendan Gongol ◽  
Indah Sari ◽  
Tiffany Bryant ◽  
Geraldine Rosete ◽  
Traci Marin
Keyword(s):  
Regulatory Elements ◽  
Dna Methyltransferases ◽  
Signaling Networks ◽  
Cellular Survival ◽  
Epigenetic Events ◽  
Dna Modifications ◽  
Health And Disease ◽  
Cellular Bioenergetics ◽  
Amp Activated Protein Kinase

Activated by AMP-dependent and -independent mechanisms, AMP-activated protein kinase (AMPK) plays a central role in the regulation of cellular bioenergetics and cellular survival. AMPK regulates a diverse set of signaling networks that converge to epigenetically mediate transcriptional events. Reversible histone and DNA modifications, such as acetylation and methylation, result in structural chromatin alterations that influence transcriptional machinery access to genomic regulatory elements. The orchestration of these epigenetic events differentiates physiological from pathophysiological phenotypes. AMPK phosphorylation of histones, DNA methyltransferases and histone post-translational modifiers establish AMPK as a key player in epigenetic regulation. This review focuses on the role of AMPK as a mediator of cellular survival through its regulation of chromatin remodeling and the implications this has for health and disease.

Mechanisms and Management of Fatigue in Health and Disease: Symposium Introduction

2004 ◽  
Vol 29 (3) ◽  
pp. 264-273 ◽  
Author(s):  
Howard J. Green
Keyword(s):  
Muscle Cell ◽  
Mechanical Response ◽  
Exercise Intolerance ◽  
Free Calcium ◽  
Neural Activation ◽  
Membrane Excitability ◽  
Cell Contractility ◽  
Health And Disease ◽  
Underlying Mechanisms

Exercise intolerance is a condition commonly experienced by both the healthy and those with disease. Yet we have only a limited understanding of the underlying mechanisms and, consequently, the management of this condition. In this Symposium, a major objective was to address the role of the muscle cell in weakness and fatigue. We have focused on addressing the advances made in characterizing the basis of muscle cell contractility with particular respect to the processes and proteins involved in excitation and contraction, and how these processes can be modified during repetitive activity. Three reviews are provided on this subject. Each addresses a specific link in the cascade of events from neural activation of the muscle to the generation of force. In the first review the processes involved in signal transduction in the sarcolemma and T-tubule, and which regulate membrane excitability, are examined. The second review analyzes the sarcoplasmic reticulum regulation of the intracellular messenger that controls the myofibrillar complex, namely free calcium. The final review in this series deals with the events regulating actin-myosin behaviour and the mechanical response. All reviews place special emphasis on how different sites can be modified by repetitive activity and, as a consequence, how they can represent a potential source of fatigue. Since it is important to understand the nature, manifestations, and measurement of weakness and fatigue, a comprehensive review on these topics is also provided. Key words: weakness, muscle, measurement, excitation, contraction

scholarly journals Mitochondrial Kinases and the Role of Mitochondrial Protein Phosphorylation in Health and Disease

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 82
Author(s):  
Veronika Kotrasová ◽  
Barbora Keresztesová ◽  
Gabriela Ondrovičová ◽  
Jacob A. Bauer ◽  
Henrieta Havalová ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Mitochondrial Protein ◽  
Structure And Function ◽  
Stress Factors ◽  
Mitochondrial Proteins ◽  
Post Translational Modification ◽  
Mitochondrial Structure ◽  
Health And Disease ◽  
And Function

The major role of mitochondria is to provide cells with energy, but no less important are their roles in responding to various stress factors and the metabolic changes and pathological processes that might occur inside and outside the cells. The post-translational modification of proteins is a fast and efficient way for cells to adapt to ever changing conditions. Phosphorylation is a post-translational modification that signals these changes and propagates these signals throughout the whole cell, but it also changes the structure, function and interaction of individual proteins. In this review, we summarize the influence of kinases, the proteins responsible for phosphorylation, on mitochondrial biogenesis under various cellular conditions. We focus on their role in keeping mitochondria fully functional in healthy cells and also on the changes in mitochondrial structure and function that occur in pathological processes arising from the phosphorylation of mitochondrial proteins.

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