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.

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 Chromosome Instability, Aging and Brain Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1256
Author(s):  
Ivan Y. Iourov ◽  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Sergei I. Kutsev
Keyword(s):  
Brain Aging ◽  
Chromosome Instability ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Brain Diseases ◽  
Aging Brain ◽  
Ontogenetic Changes ◽  
Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2547
Author(s):  
Keunsoo Kang ◽  
Yoonjung Choi ◽  
Hyeonjin Moon ◽  
Chaelin You ◽  
Minjin Seo ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Homologous Recombination ◽  
Cell Lines ◽  
Regulatory Elements ◽  
Binding Motif ◽  
Genome Wide ◽  
E Box ◽  
Autophagy Pathway ◽  
Mcf 7

RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.

scholarly journals Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle

2021 ◽  
Vol 22 (8) ◽  
pp. 3920
Author(s):  
Violetta V. Kravtsova ◽  
Inna I. Paramonova ◽  
Natalia A. Vilchinskaya ◽  
Maria V. Tishkova ◽  
Vladimir V. Matchkov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Single Injection ◽  
Chronic Administration ◽  
Motor Dysfunction ◽  
Hindlimb Suspension ◽  
Muscle Disuse ◽  
Rat Soleus Muscle ◽  
Amp Activated Protein Kinase ◽  
Specific Ligand

Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is characteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis and prevents its disuse-induced disturbances. Isolated soleus muscles from rats intraperitoneally injected with ouabain alone or subsequently exposed to muscle disuse by 6-h hindlimb suspension (HS) were studied. Conventional electrophysiology, Western blotting, and confocal microscopy with cytochemistry were used. Acutely applied 10 nM ouabain hyperpolarized the membrane. However, a single injection of ouabain (1 µg/kg) prior HS was unable to prevent the HS-induced membrane depolarization. Chronic administration of ouabain for four days did not change the α1 and α2 Na,K-ATPase protein content, however it partially prevented the HS-induced loss of the Na,K-ATPase electrogenic activity and sarcolemma depolarization. These changes were associated with increased phosphorylation levels of AMP-activated protein kinase (AMPK), its substrate acetyl-CoA carboxylase and p70 protein, accompanied with increased mRNA expression of interleikin-6 (IL-6) and IL-6 receptor. Considering the role of AMPK in regulation of the Na,K-ATPase, we suggest an IL-6/AMPK contribution to prevent the effects of chronic ouabain under skeletal muscle disuse.

scholarly journals Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Protective Effect ◽  
Histone Modification ◽  
Regulatory Networks ◽  
Target Gene ◽  
Regulatory Elements ◽  
Chromatin Interactions ◽  
Super Enhancer

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.

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