Impact of ischemia/reperfusion (IR) and sitagliptin administration on dimethylarginine dimethylaminohydrolase (DDAH) activity and protein arginine methyltransferase (PRMT) and DDAH1 mRNA expression in rat liver

2015 ◽  
Vol 67 ◽  
pp. 42
Author(s):  
Małgorzata Trocha ◽  
Anna Merwid-Ląd ◽  
Tomasz Sozański ◽  
Ewa Chlebda ◽  
Dorota Nowak ◽  
...  
2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Daniel P Harris

TNF-α initiates the expression of genes involved in the recruitment, adhesion, and transmigration of leukocytes to sites of inflammation. Here, we report that the protein arginine methyltransferase PRMT5 is required for the transcriptional induction of the pro-inflammatory chemokine CXCL10 (IP-10) in endothelial cells. Depletion of PRMT5 by siRNA results in significantly diminished TNF-α-induced CXCL10 mRNA expression, but does not affect expression of other chemokines, such as MCP-1 or IL-8. Chromatin immunoprecipitation experiments of the CXCL10 proximal promoter show the presence of symmetrical dimethylated arginine (sDMA)-containing proteins upon exposure to TNF-α. This methylation is completely lost when PRMT5 is removed from cells by siRNA. Using immunoprecipitation, we show that PRMT5 enhances CXCL10 expression by methylating the RelA (p65) subunit of NF-κB. In summary, we have identified that PRMT5 is a novel regulator of CXCL10 expression. Further, we have discovered that PRMT5 methylates NF-κB, a finding which may further knowledge of the post-translational code governing NF-κB regulation and target specificity.


2002 ◽  
Vol 320 (2) ◽  
pp. 223-235 ◽  
Author(s):  
Junichi Komoto ◽  
Yafei Huang ◽  
Yoshimi Takata ◽  
Taro Yamada ◽  
Kiyoshi Konishi ◽  
...  

2015 ◽  
Vol 27 (4) ◽  
pp. 655 ◽  
Author(s):  
Bethany K. Redel ◽  
Kimberly J. Tessanne ◽  
Lee D. Spate ◽  
Clifton N. Murphy ◽  
Randall S. Prather

Culture systems promote development at rates lower than the in vivo environment. Here, we evaluated the embryo’s transcriptome to determine what the embryo needs during development. A previous mRNA sequencing endeavour found upregulation of solute carrier family 7 (cationic amino acid transporter, y+ system), member 1 (SLC7A1), an arginine transporter, in in vitro- compared with in vivo-cultured embryos. In the present study, we added different concentrations of arginine to our culture medium to meet the needs of the porcine embryo. Increasing arginine from 0.12 to 1.69 mM improved the number of embryos that developed to the blastocyst stage. These blastocysts also had more total nuclei compared with controls and, specifically, more trophectoderm nuclei. Embryos cultured in 1.69 mM arginine had lower SLC7A1 levels and a higher abundance of messages involved with glycolysis (hexokinase 1, hexokinase 2 and glutamic pyruvate transaminase (alanine aminotransferase) 2) and decreased expression of genes involved with blocking the tricarboxylic acid cycle (pyruvate dehydrogenase kinase, isozyme 1) and the pentose phosphate pathway (transaldolase 1). Expression of the protein arginine methyltransferase (PRMT) genes PRMT1, PRMT3 and PRMT5 throughout development was not affected by arginine. However, the dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2 message was found to be differentially regulated through development, and the DDAH2 protein was localised to the nuclei of blastocysts. Arginine has a positive effect on preimplantation development and may be affecting the nitric oxide–DDAH–PRMT axis.


2001 ◽  
Vol 120 (5) ◽  
pp. A379-A379
Author(s):  
Y TAKAMATSU ◽  
K SHIMADA ◽  
K CHIJIWA ◽  
M TANAKA

2003 ◽  
Vol 124 (4) ◽  
pp. A719-A720
Author(s):  
Yuji Takamatsu ◽  
Kazuo Shimada ◽  
Koji Yamaguchi ◽  
Kazuo Chijiiwa ◽  
Masao Tanaka

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Busacca ◽  
Qi Zhang ◽  
Annabel Sharkey ◽  
Alan G. Dawson ◽  
David A. Moore ◽  
...  

AbstractWe hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation. Quinacrine phenocopied PRMT5 RNA interference and small molecule PRMT5 inhibition, reducing clonogenicity in an MTAP-dependent manner. This activity required a functional PRMT5 methyltransferase as MTAP negative cells were rescued by exogenous wild type PRMT5, but not a PRMT5E444Q methyltransferase-dead mutant. We identified c-jun as an essential PRMT5 transcription factor and a probable target for Quinacrine. Our results therefore suggest that small molecule-based transcriptional perturbation of PRMT5 can leverage a mutation-selective vulnerability, that is therapeutically tractable, and has relevance to 9p21 deleted cancers including MPM.


2021 ◽  
Vol 22 (12) ◽  
pp. 6399
Author(s):  
Ioanna Papatheodorou ◽  
Eleftheria Galatou ◽  
Georgios-Dimitrios Panagiotidis ◽  
Táňa Ravingerová ◽  
Antigone Lazou

Accumulating evidence support the cardioprotective properties of the nuclear receptor peroxisome proliferator activated receptor β/δ (PPARβ/δ); however, the underlying mechanisms are not yet fully elucidated. The aim of the study was to further investigate the mechanisms underlying PPARβ/δ-mediated cardioprotection in the setting of myocardial ischemia/reperfusion (I/R). For this purpose, rats were treated with PPARβ/δ agonist GW0742 and/or antagonist GSK0660 in vivo and hearts were subjected to ex vivo global ischemia followed by reperfusion. PPARβ/δ activation improved left ventricular developed pressure recovery, reduced infarct size (IS) and incidence of reperfusion-induced ventricular arrhythmias while it also up-regulated superoxide dismutase 2, catalase and uncoupling protein 3 resulting in attenuation of oxidative stress as evidenced by the reduction in 4-hydroxy-2-nonenal protein adducts and protein carbonyl formation. PPARβ/δ activation also increased both mRNA expression and enzymatic activity of aldehyde dehydrogenase 2 (ALDH2); inhibition of ALDH2 abrogated the IS limiting effect of PPARβ/δ activation. Furthermore, upregulation of PGC-1α and isocitrate dehydrogenase 2 mRNA expression, increased citrate synthase activity as well as mitochondrial ATP content indicated improvement in mitochondrial content and energy production. These data provide new mechanistic insight into the cardioprotective properties of PPARβ/δ in I/R pointing to ALDH2 as a direct downstream target and suggesting that PPARβ/δ activation alleviates myocardial I/R injury through coordinated stimulation of the antioxidant defense of the heart and preservation of mitochondrial function.


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