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Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Paraganglioma exhibits recurrent mutations in the succinate dehydrogenase (SDH) genes. Sdhb knockout in mouse chromaffin cells triggered a CpG island methylator phenotype, with an increased 5-mC/5-hmC ratio, and enhanced histone methylation at H3K9me3, H3K27me2, and H3K27me3 (Letouze et al., 2013). The methylome abnormalities in Sdhb knockout cells induced the transcriptional silencing of genes involved in differentiation and metastasis suppression, leading to an invasive and migratory phenotype. In independent patient cohorts, mutant SDH is associated with a DNA methylator phenotype in paraganglioma and pheochromocytoma (Letouze et al., 2013). Moreover, paragangliomas with SDH or FH deficiency associated DNA methylator phenotype had a much worse prognosis compared with other subtypes, indicating that epigenetic dysregulation promotes tumor progression. Similarly, SDH mutations in GISTs are associated with genomic methylation an order of magnitude greater than that of SDH wildtype GISTs (Killian et al., 2013). Consistent with the inhibitory effect of succinate on DNA demethylation, SDH-mutant GISTs displayed a marked loss of TET activity. In vitro studies have shown that dominant negative expression of mutant FH- or SDH-, or metabolite supplementation (succinate and fumarate) recapitulates epigenetic phenotypes of FH- and SDH-mutant cancers, which is reversed upon a-ketoglutarate supplementation, further confirming the key role of TCA cycle metabolites in regulating the epigenome via modulating DNA/histone demethylation.
Nano Carrier Systems of Ubidecarenone (Coenzyme Q10) for Cosmetic Applications
Published in Anil K. Sharma, Raj K. Keservani, Rajesh K. Kesharwani, Nanobiomaterials, 2018
N. k. Yadav, Rekha Rao, O. P. Katare, Sanju Nanda
CoQ10 is also recognized as ubiquinone-10, and acts as co-enzyme in energy-generation pathways of body cells. The major role of CoQ10 is to produce energy by acting in the form of a cofactor in mitochondrial electron transport chain (Kapoor and Kapoor, 2013). The production of energy is stored as Adenosine Triphosphate (ATP) generated from electron transport chain, which governs the cellular functions of the body. It performs a vital role in energy generation by transferring electron from Nicotinamide adenine dinucleotide phosphate (NADPH) to cytochrome complex through succinate dehydrogenase. It also perform cofactor role for electron transport enzymes which participate in oxidative phosphorylation.
Evaluation of the effect of cold atmospheric plasma on oxygenases’ activities for application in water treatment technologies
Published in Environmental Technology, 2019
Yovana Todorova, Ivaylo Yotinov, Yana Topalova, Evgenia Benova, Plamena Marinova, Ivan Tsonev, Todor Bogdanov
The benzene ring cleavage and the consecutive transformations result in key metabolic products of the tricarboxylic acid cycle (TCA). Enzymological indicator for the inclusion of metabolites in the central metabolic pathways of the cell and functioning of the TCA is the activity of succinate dehydrogenase (SDH). A simple scheme of phenol biodegradation pathways is presented in Figure 1 with the emphasis on the enzymes included in our study.