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.

• Keywords
• ACE2, embryonic heart, human kidney embryonic cells, lung cancer cells, renin,
• MeSH
• Angiotensin-Converting Enzyme 2 metabolism   MeSH
• Cell Differentiation physiology   MeSH
• A549 Cells MeSH
• HT29 Cells MeSH
• COVID-19 epidemiology   pathology   virology   MeSH
• HEK293 Cells MeSH
• Humans MeSH
• Mice MeSH
• Pandemics MeSH
• Gene Expression Regulation physiology   MeSH
• Renin-Angiotensin System physiology   MeSH
• Renin metabolism   MeSH
• SARS-CoV-2 pathogenicity   MeSH
• Sex Factors MeSH
• Aging physiology   MeSH
• Age Factors MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Angiotensin-Converting Enzyme 2 MeSH
• Renin MeSH

Polyaniline cryogel is a new unique form of polyaniline combining intrinsic electrical conductivity and the material properties of hydrogels. It is prepared by the polymerization of aniline in frozen poly(vinyl alcohol) solutions. The biocompatibility of macroporous polyaniline cryogel was demonstrated by testing its cytotoxicity on mouse embryonic fibroblasts and via the test of embryotoxicity based on the formation of beating foci within spontaneous differentiating embryonic stem cells. Good biocompatibility was related to low contents of low-molecular-weight impurities in polyaniline cryogel, which was confirmed by liquid chromatography. The adhesion and growth of embryonic stem cells, embryoid bodies, cardiomyocytes, and neural progenitors prove that polyaniline cryogel has the potential to be used as a carrier for cells in tissue engineering or bio-sensing. The surface energy as well as the elasticity and porosity of cryogel mimic tissue properties. Polyaniline cryogel can therefore be applied in bio-sensing or regenerative medicine in general, and mainly in the tissue engineering of electrically excitable tissues.

• MeSH
• Algorithms MeSH
• Aniline Compounds chemistry   MeSH
• Biocompatible Materials chemistry   MeSH
• Cell Culture Techniques MeSH
• Electric Conductivity MeSH
• Fibroblasts MeSH
• Cryogels chemistry   MeSH
• Mechanical Phenomena MeSH
• Elastic Modulus MeSH
• Mice MeSH
• Porosity MeSH
• Models, Theoretical MeSH
• Materials Testing MeSH
• Tissue Engineering MeSH
• Cell Survival MeSH
• Chromatography, High Pressure Liquid MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Aniline Compounds MeSH
• Biocompatible Materials MeSH
• Cryogels MeSH
• polyaniline MeSH Browser

Neuroblastoma is the most common extracranial solid tumour of infancy. Pathological activation of glucose consumption, glycolysis and glycolysis-activating Akt kinase occur frequently in neuroblastoma cells, and these changes correlate with poor prognosis of patients. Therefore, several inhibitors of glucose utilization and the Akt kinase activity are in preclinical trials as potential anti-cancer drugs. However, metabolic plasticity of cancer cells might undermine efficacy of this approach. In this work, we identified oxidative phosphorylation as compensatory mechanism preserving viability of neuroblastoma cells with inhibited glucose uptake/Akt kinase. It was oxidative phosphorylation that maintained intracellular level of ATP and proliferative capacity of these cells. The oxidative phosphorylation inhibitors (rotenone, tetrathiomolybdate) synergized with inhibitor of the Akt kinase/glucose uptake in down-regulation of both viability of neuroblastoma cells and clonogenic potential of cells forming neuroblastoma spheroids. Interestingly, tetrathiomolybdate acted as highly specific inhibitor of oxygen consumption and activator of lactate production in neuroblastoma cells, but not in normal fibroblasts and neuronal cells. Moreover, the reducing effect of tetrathiomolybdate on cell viability and the level of ATP in the cells with inhibited Akt kinase/glucose uptake was also selective for neuroblastoma cells. Therefore, efficient elimination of neuroblastoma cells requires inhibition of both glucose uptake/Akt kinase and oxidative phosphorylation activities. The use of tetrathiomolybdate as a mitochondrial inhibitor contributes to selectivity of this combined treatment, preferentially targeting neuroblastoma cells.

• Keywords
• Akt kinase, cell viability, glycolysis, metabolic plasticity, neuroblastoma, oxygen consumption, tetrathiomolybdate,
• MeSH
• Adenosine Triphosphate metabolism   MeSH
• Cell Respiration drug effects   MeSH
• Down-Regulation drug effects   MeSH
• Fibroblasts drug effects   metabolism   MeSH
• Phosphorylation drug effects   MeSH
• Glucose metabolism   MeSH
• Protein Kinase Inhibitors pharmacology   MeSH
• Lactic Acid biosynthesis   MeSH
• Humans MeSH
• Mitochondria drug effects   metabolism   MeSH
• Molybdenum pharmacology   MeSH
• Mice, Inbred C57BL MeSH
• Cell Line, Tumor MeSH
• Neuroblastoma enzymology   metabolism   pathology   MeSH
• Neurons drug effects   metabolism   MeSH
• Oxidative Phosphorylation drug effects   MeSH
• Proto-Oncogene Proteins c-akt antagonists & inhibitors   metabolism   MeSH
• Oxygen Consumption drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenosine Triphosphate MeSH
• Glucose MeSH
• Protein Kinase Inhibitors MeSH
• Lactic Acid MeSH
• Molybdenum MeSH
• Proto-Oncogene Proteins c-akt MeSH
• tetrathiomolybdate MeSH Browser

Cajal bodies (CBs) are important compartments containing accumulated proteins that preferentially regulate RNA-related nuclear events, including splicing. Here, we studied the nuclear distribution pattern of CBs in neurogenesis. In adult brains, coilin was present at a high density, but CB formation was absent in the nuclei of the choroid plexus of the lateral ventricles. Cells of the adult hippocampus were characterized by a crescent-like morphology of coilin protein. We additionally observed a 70 kDa splice variant of coilin in adult mouse brains, which was different to embryonic brains and mouse pluripotent embryonic stem cells (mESCs), characterized by the 80 kDa standard variant of coilin. Here, we also showed that depletion of coilin is induced during neural differentiation and HDAC1 deficiency in mESCs caused coilin accumulation inside the fibrillarin-positive region of the nucleoli. A similar distribution pattern was observed in adult brain hippocampi, characterized by lower levels of both coilin and HDAC1. In summary, we observed that neural differentiation and HDAC1 deficiency lead to coilin depletion and coilin accumulation in body-like structures inside the nucleoli.

• Publication type
• Journal Article MeSH