CARM1 i nteracts with numerous transcription factors to mediate cellular processes, especially gene expression. This is important for the maintenance of ESC pluripotency or intervention to tumorigenesis. Here, we studied epigenomic effects of two potential CARM1 m odulators: an activator (EML159) and an inhibitor (ellagic acid dihydrate, EA). We examined nuclear morphology in human and mouse embryonic stem cells (hESCs, mESCs), as well as in iPS cells. The CARM1 modulators did not function similarly in all cell type s. EA decreased the levels of the pluripotency markers, OCT4 and NANOG, particularly in iPSCs, whereas the levels of these proteins increased after EML159 treatment. EML159 treatment of mouse ESCs led to decreased levels of OCT4 and NANOG, which was accomp anied by an increased level of Endo -A. The same trend was observed for NANOG and Endo -A in hESCs affected by EML159. Interestingly, EA mainly changed epigenetic features of nucleoli because a high level of arginine asymmetric di- methylation in the nucleoli of hESCs was reduced after EA treatment. ChIP -PCR of ribosomal genes confirmed significantly reduced levels of H3R17me2a, in both the promoter region of ribosomal genes and rDNA encoding 28S rRNA, after EA addition. Moreover, EA treatment changed the nuclear pattern of AgNORs (silver -stained nucleolus organizer regions) in all cell types studied. In EA -treated ESCs, AgNOR pattern was similar to the pattern of AgNORs after inhibition of RNA pol I by actinomycin D. Together, inhibitory effect of EA on arginine methylation and effect on related morphological parameters was especially observed in compartment of nucleoli., M. Franek, S. Legartová, J. Suchánková, C. Milite, S. Castellano, G. Sbardella, S. Kozubek, E. Bártová., and Obsahuje bibliografii
The possible protective action of L-carnitine on neuronal excitability was studied in 21-day-old male Wistar rats with implanted electrodes. Administration of L-carnitine did not change the elicitation and duration of the epileptic seizures (cortical afterdischarges, ADs) in rats under normobaric oxygen atmosphere conditions. However, in animals exposed to 30 min hypobaric hypoxia the duration of the ADs was shortened after the second, fourth and sixth stimulation (in comparison with the first evoked ADs) while carnitine-treated rats retained their neuronal excitability and the duration of ADs was shortened only after the third stimulation., D. Marešová, H. Rauchová, K. Jandová, I. Valkounová, J. Koudelová, S. Trojan., and Obsahuje bibliografii
In the presence of carnosine, anserine, histidine, imidazole and 7-nitro indazole, the early postdenervation depolarization of muscle of about 8 mV was significantly increased by 2.15-4.8 mV. The presence of the imidazole ring in the molecule is apparently necessary for this effect. These compounds also eliminated an NO-mediated protective effect of L-glutamate and carbachol on the depolarization of membrane potential. The presence of imidazole, 7-nitro indazole, carnosine and anserine did not significantly change the effect of an external NO donor, sodium nitroprusside. The structural and fuhctional similarity between imidazole derivatives and the known NO synthase inhibitor, 7-nitro indazole suggests that imidazole, carnosine and anserine might act by inhibiting NO production which is stimulated by glutamate and carbachol.