scholarly journals Keeping the balance in NAD metabolism

2019 ◽  
Vol 47 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Øyvind Strømland ◽  
Marc Niere ◽  
Andrey A. Nikiforov ◽  
Magali R. VanLinden ◽  
Ines Heiland ◽  
...  
Keyword(s):  
Calcium Signalling ◽  
Research Field ◽  
Therapeutic Effects ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Signalling Molecule ◽  
Cycle Regulation ◽  
Subcellular Level ◽  
Important Signalling Molecule

Abstract Research over the last few decades has extended our understanding of nicotinamide adenine dinucleotide (NAD) from a vital redox carrier to an important signalling molecule that is involved in the regulation of a multitude of fundamental cellular processes. This includes DNA repair, cell cycle regulation, gene expression and calcium signalling, in which NAD is a substrate for several families of regulatory proteins, such as sirtuins and ADP-ribosyltransferases. At the molecular level, NAD-dependent signalling events differ from hydride transfer by cleavage of the dinucleotide into an ADP-ribosyl moiety and nicotinamide. Therefore, non-redox functions of NAD require continuous biosynthesis of the dinucleotide. Maintenance of cellular NAD levels is mainly achieved by nicotinamide salvage, yet a variety of other precursors can be used to sustain cellular NAD levels via different biosynthetic routes. Biosynthesis and consumption of NAD are compartmentalised at the subcellular level, and currently little is known about the generation and role of some of these subcellular NAD pools. Impaired biosynthesis or increased NAD consumption is deleterious and associated with ageing and several pathologies. Insults to neurons lead to depletion of axonal NAD and rapid degeneration, partial rescue can be achieved pharmacologically by administration of specific NAD precursors. Restoring NAD levels by stimulating biosynthesis or through supplementation with precursors also produces beneficial therapeutic effects in several disease models. In this review, we will briefly discuss the most recent achievements and the challenges ahead in this diverse research field.

scholarly journals Emerging Role of E2F Family in Cancer Stem Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Xie ◽  
Qin Pei ◽  
Jingyuan Li ◽  
Xue Wan ◽  
Ting Ye
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Tumor Development ◽  
Transcriptional Repressors ◽  
Cellular Processes ◽  
Damage Response ◽  
Prevent Tumor Growth ◽  
Cycle Regulation

The E2F family of transcription factors (E2Fs) consist of eight genes in mammals. These genes encode ten proteins that are usually classified as transcriptional activators or transcriptional repressors. E2Fs are important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis, the DNA damage response and apoptosis. A growing body of evidence demonstrates that cancer stem cells (CSCs) are key players in tumor development, metastasis, drug resistance and recurrence. This review focuses on the role of E2Fs in CSCs and notes that many signals can regulate the activities of E2Fs, which in turn can transcriptionally regulate many different targets to contribute to various biological characteristics of CSCs, such as proliferation, self-renewal, metastasis, and drug resistance. Therefore, E2Fs may be promising biomarkers and therapeutic targets associated with CSCs pathologies. Finally, exploring therapeutic strategies for E2Fs may result in disruption of CSCs, which may prevent tumor growth, metastasis, and drug resistance.

scholarly journals Mesenchymal stromal cells attenuate alveolar type 2 cells senescence through regulating NAMPT-mediated NAD metabolism

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaofan Lai ◽  
Shaojie Huang ◽  
Sijia Lin ◽  
Lvya Pu ◽  
Yaqing Wang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Potential ◽  
Alveolar Type ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Nad Metabolism

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive deadly fibrotic lung disease with high prevalence and mortality worldwide. The therapeutic potential of mesenchymal stem cells (MSCs) in pulmonary fibrosis may be attributed to the strong paracrine, anti-inflammatory, anti-apoptosis and immunoregulatory effects. However, the mechanisms underlying the therapeutic effects of MSCs in IPF, especially in terms of alveolar type 2 (AT2) cells senescence, are not well understood. The purpose of this study was to evaluate the role of MSCs in NAD metabolism and senescence of AT2 cells in vitro and in vivo. Methods MSCs were isolated from human bone marrow. The protective effects of MSCs injection in pulmonary fibrosis were assessed via bleomycin mouse models. The senescence of AT2 cells co-cultured with MSCs was evaluated by SA-β-galactosidase assay, immunofluorescence staining and Western blotting. NAD+ level and NAMPT expression in AT2 cells affected by MSCs were determined in vitro and in vivo. FK866 and NAMPT shRNA vectors were used to determine the role of NAMPT in MSCs inhibiting AT2 cells senescence. Results We proved that MSCs attenuate bleomycin-induced pulmonary fibrosis in mice. Senescence of AT2 cells was alleviated in MSCs-treated pulmonary fibrosis mice and when co-cultured with MSCs in vitro. Mechanistic studies showed that NAD+ and NAMPT levels were rescued in AT2 cells co-cultured with MSCs and MSCs could suppress AT2 cells senescence mainly via suppressing lysosome-mediated NAMPT degradation. Conclusions MSCs attenuate AT2 cells senescence by upregulating NAMPT expression and NAD+ levels, thus exerting protective effects in pulmonary fibrosis.

scholarly journals Epigenetic Studies of Chinese Herbal Medicine: Pleiotropic Role of DNA Methylation

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenqian Guo ◽  
Han Ma ◽  
Chong-Zhi Wang ◽  
Jin-Yi Wan ◽  
Haiqiang Yao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Herbal Medicine ◽  
Chinese Herbal Medicine ◽  
Bioactive Compound ◽  
Plant Responses ◽  
Therapeutic Effects ◽  
Health Maintenance ◽  
Cellular Processes ◽  
Chinese Herbal

Accumulating knowledge has been achieved on DNA methylation participating in numerous cellular processes and multiple human diseases; however, few studies have addressed the pleiotropic role of DNA methylation in Chinese herbal medicine (CHM). CHM has been used worldwide for the prevention and treatment of multiple diseases. Newly developed epigenetic techniques have brought great opportunities for the development of CHM. In this review, we summarize the DNA methylation studies and portray the pleiotropic role of DNA methylation in CHM. DNA methylation serves as a mediator participating in plant responses to environmental factors, and thus affecting CHM medicinal plants growth and bioactive compound biosynthesis which are vital for therapeutic effects. Furthermore, DNA methylation helps to uncover the pharmaceutical mechanisms of CHM formulae, herbs, and herbal-derived compounds. It also provides scientific validation for constitution theory and other essential issues of CHM. This newly developed field of DNA methylation is up-and-coming to address many complicated scientific questions of CHM; it thus not only promotes disease treatment but also facilitates health maintenance.

scholarly journals Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion

2020 ◽  
Vol 21 (18) ◽  
pp. 6841
Author(s):  
Mafalda Escobar-Henriques ◽  
Vincent Anton
Keyword(s):  
Membrane Fusion ◽  
Cell Cycle Regulation ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Cellular Viability ◽  
Mitochondrial Quality Control ◽  
Cellular Processes ◽  
Mitochondrial Regulation ◽  
Cycle Regulation

Cdc48/p97 is a ring-shaped, ATP-driven hexameric motor, essential for cellular viability. It specifically unfolds and extracts ubiquitylated proteins from membranes or protein complexes, mostly targeting them for proteolytic degradation by the proteasome. Cdc48/p97 is involved in a multitude of cellular processes, reaching from cell cycle regulation to signal transduction, also participating in growth or death decisions. The role of Cdc48/p97 in endoplasmic reticulum-associated degradation (ERAD), where it extracts proteins targeted for degradation from the ER membrane, has been extensively described. Here, we present the roles of Cdc48/p97 in mitochondrial regulation. We discuss mitochondrial quality control surveillance by Cdc48/p97 in mitochondrial-associated degradation (MAD), highlighting the potential pathologic significance thereof. Furthermore, we present the current knowledge of how Cdc48/p97 regulates mitofusin activity in outer membrane fusion and how this may impact on neurodegeneration.

Examining a new role for zinc in regulating calcium release in cardiac muscle

2015 ◽  
Vol 43 (3) ◽  
pp. 359-363 ◽  
Author(s):  
Samantha J. Pitt ◽  
Alan J. Stewart
Keyword(s):  
Cardiac Muscle ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Calcium Release ◽  
Biological Significance ◽  
Calcium Signalling ◽  
Signalling Molecule ◽  
Extracellular Stimuli ◽  
Recent Attention

It is well established that mammalian cells contain a small but measurable pool of free or labile zinc in the cytosol that is buffered in the high picomolar range. Recent attention has focused on the fact that this pool of free zinc has signalling effects that can be evoked through extracellular stimuli posing the question as to whether zinc should be regarded as a second messenger. Our knowledge of the targets, the biological significance and the molecular mechanisms of zinc signalling is limited but recent evidence suggests that zinc homoeostasis may be intimately linked to intracellular calcium signalling. In this review, we discuss the role of zinc as an intracellular signalling molecule with an emphasis on the potential role of zinc in shaping calcium-dynamics in cardiac muscle. We also consider the evidence that the cardiac ryanodine receptor (RyR2) is a potential zinc signalling target.

Structure, function and therapeutic implications of OB-fold proteins: A lesson from past to present

2020 ◽  
Vol 19 (5-6) ◽  
pp. 377-389
Author(s):  
Mohd Amir ◽  
Taj Mohammad ◽  
Ravins Dohare ◽  
Asimul Islam ◽  
Faizan Ahmad ◽  
...  
Keyword(s):  
Structure Function ◽  
Therapeutic Intervention ◽  
Protein Complexes ◽  
Underlying Mechanism ◽  
Therapeutic Implications ◽  
Dna Ligases ◽  
Cellular Processes ◽  
Ob Fold ◽  
Cycle Regulation

Abstract Oligonucleotide/oligosaccharide-binding (OB)-fold proteins play essential roles in the regulation of genome and its correct transformation to the subsequent generation. To maintain the genomic stability, OB-fold proteins are implicated in various cellular processes including DNA replication, DNA repair, cell cycle regulation and maintenance of telomere. The diverse functional spectrums of OB-fold proteins are mainly due to their involvement in protein–DNA and protein–protein complexes. Mutations and consequential structural alteration in the OB-fold proteins often lead to severe diseases. Here, we have investigated the structure, function and mode of action of OB-fold proteins (RPA, BRCA2, DNA ligases and SSBs1/2) in cellular pathways and their relationship with diseases and their possible use in therapeutic intervention. Due to the crucial role of OB-fold proteins in regulating the key physiological process, a detailed structural understanding in the context of underlying mechanism of action and cellular complexity offers a new avenue to target OB-proteins for therapeutic intervention.

The Effect of Resveratrol on Neurodegenerative Disorders: Possible Protective Actions Against Autophagy, Apoptosis, Inflammation and Oxidative Stress

2019 ◽  
Vol 25 (19) ◽  
pp. 2178-2191 ◽  
Author(s):  
Mohammad H. Pourhanifeh ◽  
Rana Shafabakhsh ◽  
Russel J. Reiter ◽  
Zatollah Asemi
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Neuronal Function ◽  
Beneficial Effects ◽  
Cellular Processes ◽  
And Oxidative Stress

The prevalence of neurodegenerative disorders characterized by the loss of neuronal function is rapidly increasing. The pathogenesis of the majority of these diseases is not entirely clear, but current evidence has shown the possibility that autophagy, apoptosis, inflammation and oxidative stress are involved. The present review summarizes the therapeutic effects of resveratrol on neurodegenerative disorders, based on the especially molecular biology of these diseases. The PubMed, Cochrane, Web of Science and Scopus databases were searched for studies published in English until March 30th, 2019 that contained data for the role of inflammation, oxidative stress, angiogenesis and apoptosis in the neurodegenerative disorders. There are also studies documenting the role of molecular processes in the progression of central nervous system diseases. Based on current evidence, resveratrol has potential properties that may reduce cell damage due to inflammation. This polyphenol affects cellular processes, including autophagy and the apoptosis cascade under stressful conditions. Current evidence supports the beneficial effects of resveratrol on the therapy of neurodegenerative disorders.

scholarly journals Role of microRNAs in the molecular diagnosis of cancer

2010 ◽  
Vol 1 (1) ◽  
pp. 4 ◽  
Author(s):  
Simona Giglio ◽  
Andrea Vecchione
Keyword(s):  
Unknown Origin ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Evolutionarily Conserved ◽  
Diagnosis Of Cancer ◽  
Diagnosis And Classification ◽  
Tumor Types ◽  
Cycle Regulation

MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, small non-coding RNA molecules of about 22 nucleotides in length that function as posttranscriptional gene regulators. They are involved in numerous cellular processes including development, cell differentiation, cell cycle regulation and apoptosis. There is increasing evidence to show that miRNAs are mutated or differentially expressed in many types of cancer and specific functions of the miRNAs are now becoming apparent. Here we discuss the current literature on potential usefulness of miRNAs as diagnostic markers, emphasizing the involvement of specific miRNAs in particular tumor types, highlighting their potential role in distinguishing benign from malignant tissues and/or the different subtypes of the same tumor and/or in diagnosis and classification of tumor of unknown origin.

Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

2020 ◽  
Author(s):  
Shamim Mushtaq
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Web Of Science ◽  
The Body ◽  
Main Role ◽  
Hallmarks Of Cancer ◽  
Cyclin Dependent Kinases ◽  
Tumor Studies ◽  
Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

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