Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.

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Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

Scientific Reports ◽

10.1038/s41598-018-35111-1 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 5

Author(s):

Anna K. Knight ◽

Hea Jin Park ◽

Dorothy B. Hausman ◽

Jennifer M. Fleming ◽

Victoria L. Bland ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Carbon Metabolism ◽

Methylation Status ◽

One Carbon Metabolism

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Study on the Relationship Between Folate, Dna Methylation and Esophagus Cancer

Journal of Clinical and Nursing Research ◽

10.26689/jcnr.v1i3.160 ◽

2017 ◽

Vol 1 (3) ◽

Author(s):

Huang Guiling

Keyword(s):

Dna Methylation ◽

Carbon Metabolism ◽

Early Screening ◽

Methyl Group ◽

Esophagus Cancer ◽

Multiple Factors ◽

Chinese Characteristic ◽

The World ◽

One Carbon Metabolism ◽

The Relationship

Esophagus cancer is a common malignant tumor in China, and itsprevalence rate and fatality rate are the highest in the world whoseoccurrence is related to multiple factors, including family heredity,race, gender, region, diet and so on. Esophagus cancer is the diseasewith the most Chinese characteristic. The pathogenesis of esophagusÂ cancer is very complicated, and the epigenetics in the pathogeneticÂ process has become the current research hotspot, and the reversibleÂ feature provides a new direction for the early screening, preventionÂ and treatment of esophagus cancer. DNA methylation is the mostÂ deep epigenetics in the current study, and the pattern of genomeÂ methylation is often abnormal in the cancerization of esophagusÂ cancer. The folate, as the methyl group donor, and B-vitaminsÂ related to one-carbon metabolism, shall directly influence theÂ condition of DNA methylation, give rise to the change of epigenetics,Â affect the occurrence of esophagus cancer. This paper summarizesÂ the relationship among the occurrence of esophagus cancer andÂ folate, several kinds of B-vitamins related to one-carbon metabolism,Â DNA methylation.

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Integrative modeling of tumor DNA methylation identifies a role for metabolism

10.1101/057638 ◽

2016 ◽

Author(s):

Mahya Mehrmohamadi ◽

Lucas K. Mentch ◽

Andrew G. Clark ◽

Jason W. Locasale

Keyword(s):

Dna Methylation ◽

Carbon Metabolism ◽

Methylation Status ◽

Individual Variability ◽

Early Event ◽

Large Contribution ◽

Cancer Type ◽

Relative Contribution ◽

One Carbon Metabolism ◽

Genomic Regions

AbstractDNA methylation varies across genomic regions, tissues and individuals in a population. Altered DNA methylation is common in cancer and often considered an early event in tumorigenesis. However, the sources of heterogeneity of DNA methylation among tumors remain poorly defined. Here, we capitalize on the availability of multi-platform data on thousands of molecularly-and clinically-annotated human tumors to build integrative models that identify the determinants of DNA methylation. We quantify the relative contribution of clinical and molecular factors in explaining within-cancer (inter-individual) variability in DNA methylation. We show that the levels of a set of metabolic genes involved in the methionine cycle that are constituents of one-carbon metabolism are predictive of several features of DNA methylation status in tumors including the methylation of genes that are known to drive oncogenesis. Finally, we demonstrate that patients whose DNA methylation status can be predicted from the genes in one-carbon metabolism exhibited improved survival over cases where this regulation is disrupted. To our knowledge, this study is the first comprehensive analysis of the determinants of methylation and demonstrates the surprisingly large contribution of metabolism in explaining epigenetic variation among individual tumors of the same cancer type. Together, our results illustrate links between tumor metabolism and epigenetics and outline future clinical implications.

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DNA Methylation Status in Cancer Disease: Modulations by Plant-Derived Natural Compounds and Dietary Interventions

Biomolecules ◽

10.3390/biom9070289 ◽

2019 ◽

Vol 9 (7) ◽

pp. 289 ◽

Cited By ~ 15

Author(s):

Karin Jasek ◽

Peter Kubatka ◽

Marek Samec ◽

Alena Liskova ◽

Karel Smejkal ◽

...

Keyword(s):

Dna Methylation ◽

Molecular Mechanisms ◽

Human Cancer ◽

Rapid Development ◽

Methylation Status ◽

Dna Methyltransferases ◽

Epigenetic Mechanism ◽

Preclinical Research ◽

Gene Expressions ◽

Wide Range

The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans.

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Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism

Oncogene ◽

10.1038/onc.2017.367 ◽

2017 ◽

Vol 37 (7) ◽

pp. 963-970 ◽

Cited By ~ 44

Author(s):

E Cuyàs ◽

S Fernández-Arroyo ◽

S Verdura ◽

R Á-F García ◽

J Stursa ◽

...

Keyword(s):

Dna Methylation ◽

Carbon Metabolism ◽

Global Dna Methylation ◽

One Carbon Metabolism

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Kiberbiztonság a koronavírus idején – a COVID–19 nemzetbiztonsági aspektusai

Scientia et Securitas ◽

10.1556/112.2021.00001 ◽

2021 ◽

Vol 2 (1) ◽

pp. 78-87

Author(s):

Tamás Palicz ◽

Balázs Bencsik ◽

Miklós Szócska

Keyword(s):

Cyber Security ◽

Vaccine Development ◽

Significant Risk ◽

Significant Risk Factor ◽

Distance Measures ◽

Data Traffic ◽

Home Office ◽

Emergency Case ◽

Wide Range ◽

Almost All

Összefoglaló. A COVID–19 pandémia az információbiztonság területén új kihívásokat jelentett. A távolról végzett munka különböző formái jelentős mértékben növelték az online tér biztonsági kockázatát. Nőtt a hálózatok nagysága, az adatforgalom, és azon felhasználók száma, akiknek nem volt érdemi tapasztalatuk az online térben. A járvány ideje alatt a kibertérből érkező támadások szektoronként és időszakonként eltérő intenzitásúak voltak, a támadások típusa a phishingtől a malwareken keresztül az információs zavarkeltésig széles spektrumban változott. Számos jelenségnek nemzetbiztonsági vonatkozásai is voltak. Összefoglaló cikkünkben a fenti jelenségek nemzetközi és hazai tapasztalatait összegezzük, különös figyelmet szentelve az egészségügyi rendszernek, illetve a vakcinafejlesztés kibertérből érkező fenyegetéseinek. Summary. During the COVID-19 pandemic, new challenges emerged in the field of information security and cyber security. Home office, home schooling and distance learning, or even telemedicine hit some organizations unprepared. Security risks in online space have increased significantly: the number of network endpoints and the number of computers, laptops and mobile devices have increased with network data traffic as well as the number of users who had no significant experience in online space. They appeared as a significant risk factor. This has been exacerbated, especially in healthcare, by the extremely high workload, which has made systems highly vulnerable. During the epidemic, attacks from cyberspace varied in intensity from sector to sector and period to period. Statistics from international and national organizations have shown that from the end of the first quarter of 2020, the number of cyber security incidents jumped sharply and then remained high even after a small decline. The types of attacks had an extremely wide range: from phishing through malware to misinformation, almost all types of attacks occurred. Many phenomena also had national security implications. Ransomware virus attacks on health have affected almost all health systems and reached high levels by the end of 2020 in particular. It was during the first period that, in an emergency case, there is thought to be an association between a ransomware virus attack and the death of a patient who was not admitted because of the attack. In addition to distance measures and the associated increase in cyber threats, the emerging threats related to vaccination, which is central to the fight against the epidemic, should also be highlighted. This period has shed light on how many vulnerabilities there are, from vaccine development through drug trials to delivery to vaccines and the organization of vaccines, that cybercriminals are able to attack. In order to prevent and combat these threats and attacks, and to respond appropriately, complex, multidisciplinary collaborations are needed in which security science has a privileged place. In our review article, we summarize the international and national experiences of the above phenomena, paying special attention to the health care system and the threats coming from cyberspace in vaccine development.

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Modeling folate, one-carbon metabolism, and DNA methylation

Nutrition Reviews ◽

10.1111/j.1753-4887.2008.00062.x ◽

2008 ◽

Vol 66 ◽

pp. S27-S30 ◽

Cited By ~ 35

Author(s):

Cornelia M Ulrich ◽

Michael C Reed ◽

H Frederik Nijhout

Keyword(s):

Dna Methylation ◽

Carbon Metabolism ◽

One Carbon Metabolism

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PPARγ preservation via promoter demethylation alleviates osteoarthritis in mice

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214940 ◽

2019 ◽

Vol 78 (10) ◽

pp. 1420-1429 ◽

Cited By ~ 9

Author(s):

Xiaobo Zhu ◽

Fang Chen ◽

Ke Lu ◽

Ai Wei ◽

Qing Jiang ◽

...

Keyword(s):

Dna Methylation ◽

Knockout Mice ◽

Cartilage Damage ◽

Critical Role ◽

Methylation Status ◽

Promoter Hypermethylation ◽

Dna Methyltransferases ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Peroxisome Proliferator

ObjectivesOsteoarthritis (OA) is the most common degenerative joint disease in aged population and its development is significantly influenced by aberrant epigenetic modifications of numerous OA susceptible genes; however, the precise mechanisms that DNA methylation alterations affect OA pathogenesis remain undefined. This study investigates the critical role of epigenetic PPARγ (peroxisome proliferator–activated receptor-gamma) suppression in OA development.MethodsArticular cartilage expressions of PPARγ and bioactive DNA methyltransferases (DNMTs) from OA patients and mice incurred by DMM (destabilisation of medial meniscus) were examined. DNA methylation status of both human and mouse PPARγ promoters were assessed by methylated specific PCR and/or bisulfite-sequencing PCR. OA protections by a pharmacological DNA demethylating agent 5Aza (5-Aza-2'-deoxycytidine) were compared between wild type and PPARγ knockout mice.ResultsArticular cartilages from both OA patients and DMM mice display substantial PPARγ suppressions likely due to aberrant elevations of DNMT1 and DNMT3a and consequential PPARγ promoter hypermethylation. 5Aza known to inhibit both DNMT1 and DNMT3a reversed the PPARγ promoter hypermethylation, recovered the PPARγ loss and effectively attenuated the cartilage damage in OA mice. 5Aza also inhibited the OA-associated excessive inflammatory cytokines and deficit anti-oxidant enzymes, which were blocked by a specific PPARγ inhibitor in cultured chondrocytes. Further, 5Aza-confered protections against the cartilage damage and the associated abnormalities of OA-susceptible factors were significantly abrogated in PPARγ knockout mice.ConclusionEpigenetic PPARγ suppression plays a key role in OA development and PPARγ preservation via promoter demethylation possesses promising therapeutic potentials in clinical treatment of OA and the related joint diseases.

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