scholarly journals Mitochondrial Retrograde Signalling and Metabolic Alterations in the Tumour Microenvironment

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 275 ◽  
Author(s):  
Dongki Yang ◽  
Jaehong Kim
Keyword(s):  
Molecular Mechanisms ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Metabolic Alterations ◽  
Retrograde Signalling ◽  
Functional Modulation

This review explores the molecular mechanisms that may be responsible for mitochondrial retrograde signalling related metabolic reprogramming in cancer and host cells in the tumour microenvironment and provides a summary of recent updates with regard to the functional modulation of diverse cells in the tumour microenvironment.

scholarly journals MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2525
Author(s):  
Jorlan Fernandes ◽  
Renan Lyra Miranda ◽  
Elba Regina Sampaio de Lemos ◽  
Alexandro Guterres
Keyword(s):  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Mirna Expression Profile ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Emerging Viruses ◽  
Cellular Mirnas ◽  
Host Interactions ◽  
Causative Agents

Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.

scholarly journals Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiforme

2019 ◽  
Vol 53 (4) ◽  
pp. 397-406 ◽  
Author(s):  
Miha Koprivnikar Kranjc ◽  
Metka Novak ◽  
Richard G. Pestell ◽  
Tamara T. Lah
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Stem Cells ◽  
Brain Tumour ◽  
Molecular Mechanisms ◽  
Tumour Microenvironment ◽  
Host Cells ◽  
Metastatic Colon Cancer ◽  
Tumour Heterogeneity ◽  
Glioblastoma Stem Cell

Abstract Background Glioblastoma is the most frequent and aggressive brain tumour in humans with median survival from 12 to 15 months after the diagnosis. This is mostly due to therapy resistant glioblastoma stem cells in addition to intertumour heterogeneity that is due to infiltration of a plethora of host cells. Besides endothelial cells, mesenchymal stem cells and their differentiated progenies, immune cells of various differentiation states, including monocytes, comprise resident, brain tumour microenvironment. There are compelling evidence for CCL5/CCR5 in the invasive and metastatic behaviour of many cancer types. CCR5, a G-protein coupled receptor, known to function as an essential co-receptor for HIV entry, is now known to participate in driving tumour heterogeneity, the formation of cancer stem cells and the promotion of cancer invasion and metastasis. Clinical trials have recently opened targeting CCR5 using a humanized monoclonal antibody (leronlimab) for metastatic triple negative breast cancer (TNBC) or a small molecule inhibitor (maraviroc) for metastatic colon cancer. There are important CCL5 and CCR5 structure and signalling mechanisms in glioblastoma. In addition, the CCL5/CCR5 axis directs infiltration and interactions with monocytes/macrophages and mesenchymal stem cells, comprising glioblastoma stem cell niches. Conclusions CCR5 is highly expressed in glioblastoma and is associated with poor prognosis of patients. CCL5/CCR5 is suggested to be an excellent new target for glioblastoma therapy. The molecular mechanisms, by which chemoattractant and receptor respond within the complex tissue microenvironment to promote cancer stem cells and tumour heterogeneity, should be considered in forthcoming studies.

scholarly journals Shifting the feeding of mice to the rest phase creates metabolic alterations, which, on their own, shift the peripheral circadian clocks by 12 hours

2015 ◽  
Vol 112 (48) ◽  
pp. E6683-E6690 ◽  
Author(s):  
Atish Mukherji ◽  
Ahmad Kobiita ◽  
Pierre Chambon
Keyword(s):  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Active Phase ◽  
Camp Response Element Binding ◽  
Circadian Clocks ◽  
Metabolic Reprogramming ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Alterations ◽  
Element Binding Protein

The molecular mechanisms underlying the events through which alterations in diurnal activities impinge on peripheral circadian clocks (PCCs), and reciprocally how the PCCs affect metabolism, thereby generating pathologies, are still poorly understood. Here, we deciphered how switching the diurnal feeding from the active to the rest phase, i.e., restricted feeding (RF), immediately creates a hypoinsulinemia during the active phase, which initiates a metabolic reprogramming by increasing FFA and glucagon levels. In turn, peroxisome proliferator-activated receptor alpha (PPARα) activation by free fatty acid (FFA), and cAMP response element-binding protein (CREB) activation by glucagon, lead to further metabolic alterations during the circadian active phase, as well as to aberrant activation of expression of the PCC components nuclear receptor subfamily 1, group D, member 1 (Nr1d1/RevErbα), Period (Per1 and Per2). Moreover, hypoinsulinemia leads to an increase in glycogen synthase kinase 3β (GSK3β) activity that, through phosphorylation, stabilizes and increases the level of the RevErbα protein during the active phase. This increase then leads to an untimely repression of expression of the genes containing a RORE DNA binding sequence (DBS), including the Bmal1 gene, thereby initiating in RF mice a 12-h PCC shift to which the CREB-mediated activation of Per1, Per2 by glucagon modestly contributes. We also show that the reported corticosterone extraproduction during the RF active phase reflects an adrenal aberrant activation of CREB signaling, which selectively delays the activation of the PPARα–RevErbα axis in muscle and heart and accounts for the retarded shift of their PCCs.

High Altitude hypoxia

2020 ◽  
Vol 17 ◽  
Author(s):  
Asma Babar ◽  
Kifayatullah Mengal ◽  
Abdul Hanan Babar ◽  
Shixin Wu ◽  
Mujahid Ali Shah ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
High Altitude ◽  
Molecular Mechanisms ◽  
Strong Association ◽  
Haemoglobin Concentration ◽  
Metabolic Reprogramming ◽  
Molecular Networks ◽  
Whole Genome ◽  
Gene Expressions ◽  
Transcriptional Responses

: The world highest and largest altitude area is called the Qinghai-Tibetan plateau (QTB), which harbors unique animal and plant species. Mammals that inhabit the higher altitude regions have adapted well to the hypoxic conditions. One of the main stressors at high altitude is hypoxia. Metabolic responses to hypoxia play important roles in cell survival strategies and some diseases. However, the homeostatic alterations that equilibrate variations in the demand and supply of energy to maintain organismal function in a prolonged low O2 environment persist partly understood, making it problematic to differentiate adaptive from maladaptive responses in hypoxia. Tibetans and yaks are two perfect examples innate to the plateau for high altitude adaptation. By the scan of the whole-genome, EPAS1 and EGLN1 were identified as key genes associated with sustained haemoglobin concentration in high altitude mammals for adaptation. The yak is a much more ancient mammal which has existed on QTB longer than humans, it is, therefore, possible that natural selection represented a diverse group of genes/pathways in yaks. Physiological characteristics are extremely informative in revealing molecular networks associated with inherited adaptation, in addition to the whole-genome adaptive changes at the DNA sequence level. Gene-expression can be changed by a variety of signals originating from the environment, and hypoxia is the main factor amongst them. The hypoxia-inducible factors (HIF-1α and EPAS1/HIF-2α) are the main regulators of oxygen in homeostasis which play a role as maestro regulators of adaptation in hypoxic reaction of molecular mechanisms. (Vague) The basis of this review is to present recent information regarding the molecular mechanism involved in hypoxia that regulates candidate genes and proteins. Many transcriptional responses toward hypoxia are facilitated by HIFs that change the number of gene expressions and help in angiogenesis, erythropoiesis, metabolic reprogramming and metastasis. HIFs also activate several signals highlighting a strong association between hypoxia, the misfolded proteins’ accumulation in the endoplasmic reticulum in stress and activation of unfolded protein response (UPR). It was observed that at high-altitude, pregnancies yield a low birth weight ∼100 g per1000 m of the climb. (Vague) It may involve variation in the events of energy-demanding, like protein synthesis. Prolonged hypobaric hypoxia causes placental ER stress, which in turn, moderates protein synthesis and reduces proliferation. Further, Cardiac hypertrophy by cytosolic Ca2+ raises and Ca2+/calmodulin, calcineurin stimulation, NF-AT3 pathway might be caused by an imbalance in Sarcoplasmic reticulum ER Ca2, might be adaptive in beginning but severe later.

scholarly journals Xyloglucan processing machinery in Xanthomonas pathogens and its role in the transcriptional activation of virulence factors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Plinio S. Vieira ◽  
Isabela M. Bonfim ◽  
Evandro A. Araujo ◽  
Ricardo R. Melo ◽  
Augusto R. Lima ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Citrus Canker ◽  
Effector Proteins ◽  
Glycoside Hydrolases ◽  
Host Cells ◽  
System A ◽  
Enzymatic Machinery

AbstractXyloglucans are highly substituted and recalcitrant polysaccharides found in the primary cell walls of vascular plants, acting as a barrier against pathogens. Here, we reveal that the diverse and economically relevant Xanthomonas bacteria are endowed with a xyloglucan depolymerization machinery that is linked to pathogenesis. Using the citrus canker pathogen as a model organism, we show that this system encompasses distinctive glycoside hydrolases, a modular xyloglucan acetylesterase and specific membrane transporters, demonstrating that plant-associated bacteria employ distinct molecular strategies from commensal gut bacteria to cope with xyloglucans. Notably, the sugars released by this system elicit the expression of several key virulence factors, including the type III secretion system, a membrane-embedded apparatus to deliver effector proteins into the host cells. Together, these findings shed light on the molecular mechanisms underpinning the intricate enzymatic machinery of Xanthomonas to depolymerize xyloglucans and uncover a role for this system in signaling pathways driving pathogenesis.

scholarly journals Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Combination Therapies ◽  
Low Oxygen ◽  
Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

scholarly journals A Metabolic Choreography of Maize Plants Treated with a Humic Substance-Based Biostimulant under Normal and Starved Conditions

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 403
Author(s):  
Kgalaletso Othibeng ◽  
Lerato Nephali ◽  
Anza-Tshilidzi Ramabulana ◽  
Paul Steenkamp ◽  
Daniel Petras ◽  
...  
Keyword(s):  
Humic Substance ◽  
Metabolic Networks ◽  
Molecular Mechanisms ◽  
Plant Cell Wall ◽  
Growth Promotion ◽  
Redox Homeostasis ◽  
Metabolic Reprogramming ◽  
Sustainable Food ◽  
Crop Development ◽  
Maize Plants

Humic substance (HS)-based biostimulants show potentials as sustainable strategies for improved crop development and stress resilience. However, cellular and molecular mechanisms governing the agronomically observed effects of HS on plants remain enigmatic. Here, we report a global metabolic reprogramming of maize leaves induced by a humic biostimulant under normal and nutrient starvation conditions. This reconfiguration of the maize metabolism spanned chemical constellations, as revealed by molecular networking approaches. Plant growth and development under normal conditions were characterized by key differential metabolic changes such as increased levels of amino acids, oxylipins and the tricarboxylic acid (TCA) intermediate, isocitric acid. Furthermore, under starvation, the humic biostimulant significantly impacted pathways that are involved in stress-alleviating mechanisms such as redox homeostasis, strengthening of the plant cell wall, osmoregulation, energy production and membrane remodelling. Thus, this study reveals that the humic biostimulant induces a remodelling of inter-compartmental metabolic networks in maize, subsequently readjusting the plant physiology towards growth promotion and stress alleviation. Such insights contribute to ongoing efforts in elucidating modes of action of biostimulants, generating fundamental scientific knowledge that is necessary for development of the biostimulant industry, for sustainable food security.

scholarly journals Metabolic reprogramming and epigenetic modifications on the path to cancer

2021 ◽  
Author(s):  
Linchong Sun ◽  
Huafeng Zhang ◽  
Ping Gao
Keyword(s):  
Immune Cells ◽  
Immune Escape ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Metabolic Reprogramming ◽  
Epigenetic Alterations ◽  
Metabolic Alterations ◽  
Cancer Hallmarks ◽  
Epigenetic Remodeling ◽  
Spatial Regionalization

AbstractMetabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.

scholarly journals Regulation of Metabolic Reprogramming by Long Non-Coding RNAs in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3485
Author(s):  
Assunta Sellitto ◽  
Giovanni Pecoraro ◽  
Giorgio Giurato ◽  
Giovanni Nassa ◽  
Francesca Rizzo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cancer Cells ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Metabolic Alterations ◽  
Cell Proliferation And Differentiation ◽  
Non Coding Rna ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Additional Level

Metabolic reprogramming is a well described hallmark of cancer. Oncogenic stimuli and the microenvironment shape the metabolic phenotype of cancer cells, causing pathological modifications of carbohydrate, amino acid and lipid metabolism that support the uncontrolled growth and proliferation of cancer cells. Conversely, metabolic alterations in cancer can drive changes in genetic programs affecting cell proliferation and differentiation. In recent years, the role of non-coding RNAs in metabolic reprogramming in cancer has been extensively studied. Here, we review this topic, with a focus on glucose, glutamine, and lipid metabolism and point to some evidence that metabolic alterations occurring in cancer can drive changes in non-coding RNA expression, thus adding an additional level of complexity in the relationship between metabolism and genetic programs in cancer cells.

scholarly journals Regulation of Osteoclast Differentiation and Activity by Lipid Metabolism

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 89
Author(s):  
Haemin Kim ◽  
Brian Oh ◽  
Kyung-Hyun Park-Min
Keyword(s):  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Bone Cells ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Metabolic Reprogramming ◽  
Lipid Lowering ◽  
Metabolic Bone Diseases ◽  
Increased Risk

Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.

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