scholarly journals The JmjC Domain Histone Demethylase Ndy1 Regulates Redox Homeostasis and Protects Cells from Oxidative Stress

2008 ◽  
Vol 28 (24) ◽  
pp. 7451-7464 ◽  
Author(s):  
Christos Polytarchou ◽  
Raymond Pfau ◽  
Maria Hatziapostolou ◽  
Philip N. Tsichlis
Keyword(s):  
Redox Regulation ◽  
Replicative Senescence ◽  
Redox Homeostasis ◽  
Histone H3 ◽  
Quinone Oxidoreductase ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Jmjc Domain ◽  
Peptidase Inhibitor ◽  
Induced Apoptosis

ABSTRACT The histone H3 demethylase Ndy1/KDM2B protects cells from replicative senescence. Changes in the metabolism of reactive oxygen species (ROS) are important for establishing senescence, suggesting that Ndy1 may play a role in redox regulation. Here we show that Ndy1 protects from H2O2-induced apoptosis and G2/M arrest and inhibits ROS-mediated signaling and DNA damage, while knockdown of Ndy1 has the opposite effects. Consistent with these observations, whereas Ndy1 overexpression promotes H2O2 detoxification, Ndy1 knockdown inhibits it. Ndy1 promotes the expression of genes encoding the antioxidant enzymes aminoadipic semialdehyde synthase (Aass), NAD(P)H quinone oxidoreductase-1 (Nqo1), peroxiredoxin-4 (Prdx4), and serine peptidase inhibitor b1b (Serpinb1b) and represses the expression of interleukin-19. At least two of these genes (Nqo1 and Prdx4) are regulated directly by Ndy1, which binds to specific sites within their promoters and demethylates promoter-associated histone H3 dimethylated at K36 and histone H3 trimethylated at K4. Simultaneous knockdown of Aass, Nqo1, Prdx4, and Serpinb1b in Ndy1-expressing cells to levels equivalent to those detected in control cells was sufficient to suppress the Ndy1 redox phenotype.

Aging alters histone H3 lysine 4 methylation in mouse germinal vesicle stage oocytes

2015 ◽  
Vol 27 (2) ◽  
pp. 419 ◽  
Author(s):  
Gen-Bao Shao ◽  
Jie Wang ◽  
Liu-Ping Zhang ◽  
Chao-Yang Wu ◽  
Jie Jin ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Histone H3 ◽  
Germinal Vesicle ◽  
Retinol Binding Protein ◽  
Oocyte Competence ◽  
Protein Levels ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Maternal Aging ◽  
Old Mice

Decreasing oocyte competence with maternal aging is a major factor in mammalian infertility. One of the factors contributing to this infertility is changes to chromatin modifications, such as histone acetylation in old MII stage oocytes. Recent studies indicate that changes in histone acetylation at MII arise at the germinal vesicle (GV) stage. We hypothesised that histone methylation could also change in old GV oocytes. To test this hypothesis, we examined mono-, di- and trimethylation of histone H3 lysine 4 (H3K4 me1, me2 and me3, respectively) in young and older oocytes from 6–8- and 42–44-week-old mice, respectively. We found that H3K4 me2 and me3 decreased in older compared with young GV oocytes (100% vs 81% and 100% vs 87%, respectively; P < 0.05). H3K4 me2 later increased in older MII oocytes (21% vs 56%; P < 0.05). We also examined the expression of genes encoding the H3K4 demethylases lysine (K)-specific demethylase 1A (Kdm1a) and retinol binding protein 2 (Rbp2). Expression of Kdm1a increased at both the mRNA and protein levels in older GV oocytes, but decreased in older MII oocytes (P < 0.05), and was negatively correlated with H3K4 me2 levels. Conversely, expression of Rbp2 mRNA and protein decreased in older GV oocytes (P < 0.05), and this was not correlated with H3K4 me3 levels. Finally, we showed that inhibition of Kdm1a of older oocytes at the GV stage restored levels of H3K4 me2 at the MII stage to those seen in ‘young’ oocytes (41% vs 38%; P > 0.05). These results suggest that changes in expression of H3K4 me2 and Kdm1a in older GV oocytes may represent a molecular mechanism underlying human infertility caused by aging.

scholarly journals Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4155
Author(s):  
Vyacheslav Buko ◽  
Ilya Zavodnik ◽  
Grażyna Budryn ◽  
Małgorzata Zakłos-Szyda ◽  
Elena Belonovskaya ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
High Fat Diet ◽  
Redox Homeostasis ◽  
Therapeutic Effects ◽  
High Fat ◽  
Regulation Of Expression ◽  
Alcoholic Steatohepatitis ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Liver Triglycerides

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.

A Chromatin-Associated Histone H3 Dementhylase Promotes the Immortalization of MEFs and the Cycling of HSC-Like Cells in Culture.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 96-96
Author(s):  
Raymond Pfau ◽  
Alexandros Tzatsos ◽  
Susan E. Bear ◽  
Christos Polytarchou ◽  
Sotirios Kampranis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Replicative Senescence ◽  
Bone Marrow Cells ◽  
Integration Site ◽  
Es Cells ◽  
High Titer ◽  
Histone H3 ◽  
Hematopoietic Stem ◽  
Jmjc Domain

Abstract A common integration site, cloned from MoMuLV-induced rat T cell lymphomas was mapped immediately upstream of Ndy1, a gene expressed primarily in ES cells, hematopoietic stem cells, testis, spleen and thymus. Ndy1 encodes a chromatin-associated nuclear protein. Ndy1 and its homolog Ndy2, which is also a target of provirus integration in retrovirus-induced lymphomas, encode proteins that were recently shown to possess JmjC-dependent histone H3 demethylase activity. Mouse embryo fibroblasts (MEFs) engineered to express Ndy1 or Ndy2 undergo immortalization in the absence of replicative senescence via a JmjC domain-dependent process. Knock down of endogenous Ndy1 or expression of JmjC domain mutants of Ndy1 promotes senescence, suggesting that Ndy1 is a physiological inhibitor of senescence in dividing cells. Infection of bone marrow cells with a high titer MigR1/Ndy1 retrovirus led to the reproducible isolation of immortalized cultures that have the phenotypic characteristics of hematopoietic stem cells. We conclude that Ndy-mediated demethylation of histone H3, promotes cell immortalization, oncogenesis and the cycling of stem cells.

scholarly journals NtbHLH1, a JAF13-like bHLH, interacts with NtMYB6 to enhance proanthocyanidin accumulation in Chinese Narcissus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuxin Fan ◽  
Jiayu Peng ◽  
Jiacheng Wu ◽  
Ping Zhou ◽  
Ruijie He ◽  
...  
Keyword(s):  
Flavonoid Biosynthesis ◽  
Transcriptional Level ◽  
Flavonoid Pathway ◽  
Regulation Of Expression ◽  
Over Expression ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Regulatory Complex ◽  
Positive Regulators ◽  
R2r3 Myb

Abstract Background Flavonoid biosynthesis in plants is primarily regulated at the transcriptional level by transcription factors modulating the expression of genes encoding enzymes in the flavonoid pathway. One of the most studied transcription factor complexes involved in this regulation consists of a MYB, bHLH and WD40. However, in Chinese Narcissus (Narcissus tazetta L. var. chinensis), a popular monocot bulb flower, the regulatory mechanism of flavonoid biosynthesis remains unclear. Results In this work, genes related to the regulatory complex, NtbHLH1 and a R2R3-MYB NtMYB6, were cloned from Chinese Narcissus. Phylogenetic analysis indicated that NtbHLH1 belongs to the JAF13 clade of bHLH IIIf subgroup, while NtMYB6 was highly homologous to positive regulators of proanthocyanidin biosynthesis. Both NtbHLH1 and NtMYB6 have highest expression levels in basal plates of Narcissus, where there is an accumulation of proanthocyanidin. Ectopic over expression of NtbHLH1 in tobacco resulted in an increase in anthocyanin accumulation in flowers, and an up-regulation of expression of the endogenous tobacco bHLH AN1 and flavonoid biosynthesis genes. In contrast, the expression level of LAR gene was significantly increased in NtMYB6-transgenic tobacco. Dual luciferase assays showed that co-infiltration of NtbHLH1 and NtMYB6 significantly activated the promoter of Chinese Narcissus DFR gene. Furthermore, a yeast two-hybrid assay confirmed that NtbHLH1 interacts with NtMYB6. Conclusions Our results suggest that NtbHLH1 may function as a regulatory partner by interacting directly with NtMYB6 to enhance proanthocyanidin accumulation in Chinese Narcissus.

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