ACE2 was observed as the cell surface receptor of the SARS-CoV-2 virus. Interestingly, we also found ACE2 positivity inside the cell nucleus. The ACE2 levels changed during cell differentiation and aging and varied in distinct cell types. We observed ACE2 depletion in the aortas of aging female mice, similarly, the aging caused ACE2 decrease in the kidneys. Compared with that in the heart, brain and kidneys, the ACE2 level was the lowest in the mouse lungs. In mice exposed to nicotine, ACE2 was not changed in olfactory bulbs but in the lungs, ACE2 was upregulated in females and downregulated in males. These observations indicate the distinct gender-dependent properties of ACE2. Differentiation into enterocytes, and cardiomyocytes, caused ACE2 depletion. The cardiomyogenesis was accompanied by renin upregulation, delayed in HDAC1-depleted cells. In contrast, vitamin D2 decreased the renin level while ACE2 was upregulated. Together, the ACE2 level is high in non-differentiated cells. This protein is more abundant in the tissues of mouse embryos and young mice in comparison with older animals. Mostly, downregulation of ACE2 is accompanied by renin upregulation. Thus, the pathophysiology of COVID-19 disease should be further studied not only by considering the ACE2 level but also the whole renin-angiotensin system.

• MeSH
• angiotensin-konvertující enzym 2 metabolismus   MeSH
• buněčná diferenciace fyziologie   MeSH
• buňky A549 MeSH
• buňky HT-29 MeSH
• COVID-19 epidemiologie   patologie   virologie   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• myši MeSH
• pandemie MeSH
• regulace genové exprese fyziologie   MeSH
• renin-angiotensin systém fyziologie   MeSH
• renin metabolismus   MeSH
• SARS-CoV-2 patogenita   MeSH
• sexuální faktory MeSH
• stárnutí fyziologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Nuclear locations of the c-myc gene and its transcripts (c-myc (T)) have been investigated in relation to nuclear domains involved in RNA synthesis and processing. Transcription of the c-myc gene appears to be linked to the late G(1)- and preferentially to S-phases of the cell cycle. The c-myc gene and its transcripts were positioned non-randomly within the interphase nucleus; additionally, c-myc RNA signals accumulated at nucleoli. Using oligo-probes, designed to exon II and exon III of the c-myc gene, single c-myc (T) was preferentially observed in human carcinoma HT29 and A549 cells. Conversely, human embryonal teratocarcinoma NTERA cells were characterized by the presence of multiple c-myc RNA signals located in both the nucleoli and nucleoplasm. When accumulated at nucleoli, c-myc (T) occupied the periphery of this organelle, though not those associated with the cultivation surface. In HT29 cells, approximately 80% of c-myc (T) co-localized with the RNAP II positive regions, so-called transcription factories. However, in approximately 20% of the cells with c-myc transcripts, the c-myc (T) was released from the site of synthesis, and was not associated with either transcription factories or SC35 domains. In approximately 60% of nuclei with c-myc (T), these signals were located in close proximity to the SC35 regions, but promyelocytic leukaemia bodies were associated with c-myc (T) only in approximately 20% of the nuclei. Taken together, c-myc RNA signals were positioned in the most internal parts of the cell nuclei preferentially associated with the nucleoli. Specific nuclear and nucleolar positioning probably reflects the kinetics of c-myc RNA metabolism.

• MeSH
• buněčné jádro genetika   metabolismus   ultrastruktura   MeSH
• buňky HT-29 MeSH
• exprese genu MeSH
• financování organizované MeSH
• genetická transkripce MeSH
• geny myc MeSH
• lidé MeSH
• lidské chromozomy, pár 8 MeSH
• messenger RNA metabolismus   MeSH
• nádorové buňky kultivované MeSH
• protoonkogenní proteiny c-myc metabolismus   MeSH
• RNA-polymerasa II metabolismus   MeSH
• tkáňová distribuce MeSH
• Check Tag
• lidé MeSH

The effects of the histone deacetylase inhibitors (HDACi) trichostatin A (TSA) and sodium butyrate (NaBt) were studied in A549, HT29 and FHC human cell lines. Global histone hyperacetylation, leading to decondensation of interphase chromatin, was characterized by an increase in H3(K9) and H3(K4) dimethylation and H3(K9) acetylation. The levels of all isoforms of heterochromatin protein, HP1, were reduced after HDAC inhibition. The observed changes in the protein levels were accompanied by changes in their interphase patterns. In control cells, H3(K9) acetylation and H3(K4) dimethylation were substantially reduced to a thin layer at the nuclear periphery, whereas TSA and NaBt caused the peripheral regions to become intensely acetylated at H3(K9) and dimethylated at H3(K4). The dispersed pattern of H3(K9) dimethylation was stable even at the nuclear periphery of HDACi-treated cells. After TSA and NaBt treatment, the HP1 proteins were repositioned more internally in the nucleus, being closely associated with interchromatin compartments, while centromeric heterochromatin was relocated closer to the nuclear periphery. These findings strongly suggest dissociation of HP1 proteins from peripherally located centromeres in a hyperacetylated and H3(K4) dimethylated environment. We conclude that inhibition of histone deacetylases caused dynamic reorganization of chromatin in parallel with changes in its epigenetic modifications.

• MeSH
• apoptóza účinky záření   MeSH
• buněčné jádro enzymologie   genetika   metabolismus   účinky léků   MeSH
• buněčné linie MeSH
• buněčný cyklus účinky léků   MeSH
• buňky HT-29 MeSH
• chromatin metabolismus   MeSH
• chromozomální proteiny, nehistonové antagonisté a inhibitory   metabolismus   MeSH
• financování organizované MeSH
• histondeacetylasy metabolismus   MeSH
• histony metabolismus   MeSH
• inhibitory enzymů farmakologie   MeSH
• inhibitory histondeacetylas MeSH
• interfáze účinky léků   MeSH
• kyselina máselná farmakologie   MeSH
• kyseliny hydroxamové farmakologie   MeSH
• lidé MeSH
• malobuněčný karcinom enzymologie   metabolismus   patologie   MeSH
• nádorové buněčné linie MeSH
• nádory plic enzymologie   metabolismus   patologie   MeSH
• nádory tračníku enzymologie   metabolismus   patologie   MeSH
• plod MeSH
• Check Tag
• lidé MeSH