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Cíl studie: V reprodukčním období ženy dochází k opakovaným a častým strukturálním a funkčním proměnám endometria. Schopnost regenerace, remodelace a diferenciace je předpokladem receptivity endometria, implantace a vývoje embrya. Důležitým faktorem těchto procesů je vzájemná přeměna mezenchymálního a epiteliálního fenotypu endometriálních buněk – epiteliálně- -mezenchymální transice (EMT = epitelial-mesenchymal transition) a mezenchymálně-epiteliální transice (MET = mesenchymal-epithelial transition). Cílem práce je prezentovat současné poznatky o vzájemné přeměně epiteliálních a mezenchymální buněk děložní sliznice a jejich možném vlivu na poruchy plodnosti. Typ studie: Přehledová práce. Název a sídlo pracoviště: Gynekologicko-porodnická klinika Lékařské fakulty Masarykovy univerzity a FN Brno; Porodnicko-gynekologická klinika FN a LF UP Olomouc. Metodika: Literární rešerše databáze PubMed publikované do února 2019 s termíny zaměřenými na „endometrial receptivity“, „embryo implantation“, „endometrial regeneration“, „mesenchymal–epithelial transition/transformation“. Výsledky: Bylo prokázáno, že stromální buňky se podílejí na regeneraci nejen stromatu, ale také epitelu endometria. V průběhu decidualizace působením ovariálních steroidů a dalších faktorů probíhá MET, fibroblasty stromatu získávají postupně vlastnosti epiteliálních buněk – morfologicky i funkčně (sekreční endoplazmatické retikulum, pevné intercelulární spoje). V průběhu implantace embrya vlivem interakce trofoblastu s decidualizovaným endometriem dochází k přeměně epiteliálních buněk na mezenchymální (EMT), které jsou schopny migrace a regulace pronikajícího trofoblastu. Závěr: Vzájemná přeměna stromálních a epiteliálních buněk endometria je nezbytná pro fyziologickou funkci děložní sliznice včetně implantace a vývoje embrya.
Objective: During reproductive age of a woman, endometrium undergoes frequent stuctural and functional changes. Abilities of regeneration, remodelation and differentiation are precondition of endometrial receptivity and implantation and development of an embryo. These processes are conditioned by mutual transformation between mesenchymal and epithelial fenotype of endometrial cells: epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). The aim of this study is to present contemporary knowledge of transformation between epithelial and mesenchymal endometrial cells and its influence on human fertility. Design: Review article. Setting: Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk university and University Hospital Brno; Department of Obstetrics and Gynecology, University Hospital Faculty of Medicine, Palacky University, Olomouc. Methods: PubMed was searched for articles in English indexed until February 2019 with terms of „endometrial receptivity“, „embryo implantation“, „endometrial regeneration“, „mesenchymal-epithelial transition/ transformation“. Results: It has been proved, that mesenchymal stromal cells participate on regeneration of not only the endometrial stroma, but also of the epithelium. During endometrial decidualisation under influence of ovarian steroids, the MET is under way. Stromal fibroblasts gain the morfological and functional properties of epithelial cells. During implantaion of an embryo, the trofoblast interacts with decidualised endometrium. Epithelial cells transform into mesenchymal (EMT), which mediate the growth of trofoblast. Conclusion: Mutual transformation between stromal and epithelial cells in essential for normal function of endometrium and implantation and development of an embryo.
- Klíčová slova
- mezenchymálněepiteliální transformace buněk, receptivita endometria, regenerace endometria,
- MeSH
- endometrium * fyziologie MeSH
- implantace embrya MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Abstract Reproductive period in woman is characterized by cyclic changes of endometrium and its regeneration. The factors important for proper function of the endometrium are anatomical structure, hormonal control and signalling pathways on molecular-genetic level. New knowledge on uterine microbiome, mutual epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) of endometrial cells refine our conception of changes on cellular level, endometrial receptivity and possible causes of endometrial dysfunction. Substantial information on bacterial colonisation of endometrium were discovered by new diagnostic methods using analysis of ribosomal RNA in 16S subunit which are able to detect and exactly identify bacteria that are not detectable by classic cultivation methods. Endometrial microbiome prevents development of pathogenous microorganisms and modulates function of endometrial cells. It has been proven that stromal cells contribute to regeneration of not only the endometrial stroma, but also of the epithelium. Activity of ovarian steroids and other factors leads to EMT/MET, which ensures different functions of endometrium throughout the menstrual cycle and pregnancy. The endometrial microbiome and mutual transition of stromal and epithelial endometrial cells are necessary for physiological functions of uterine mucosa including implantation and development of an embryo. Running title : Microbiome and cells transition in endometrial function
- Publikační typ
- časopisecké články MeSH
Values of the calcium retention capacity (CRC) of rat liver mitochondria are highly dependent on the experimental conditions used. When increasing amounts of added calcium chloride are used (1.25-10 nmol), the values of the CRC increase 3-fold. When calcium is added in 75 s intervals, the CRC values increase by 30 % compared with 150 s interval additions. CRC values are not dependent on the calcium/protein ratio in the measured sample in our experimental design. We also show that a more detailed evaluation of the fluorescence curves can provide new information about mitochondrial permeability transition pore opening after calcium is added.
- MeSH
- biologický transport MeSH
- jaterní mitochondrie metabolismus MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- mitochondriální membrány metabolismus MeSH
- permeabilita MeSH
- přechodový pór mitochondriální permeability metabolismus MeSH
- transportní proteiny mitochondriální membrány metabolismus MeSH
- vápník metabolismus MeSH
- výzkumný projekt MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
3 s. ; 30 cm
- MeSH
- služby zdravotní péče o pracující trendy MeSH
- socioekonomické faktory MeSH
- Geografické názvy
- Evropa MeSH
- Konspekt
- Veřejné zdraví a hygiena
- NLK Obory
- management, organizace a řízení zdravotnictví
- věda a výzkum
- NLK Publikační typ
- publikace WHO
Mitochondria play an important role in the cell aging process. Changes in calcium homeostasis and/or increased reactive oxygen species (ROS) production lead to the opening of mitochondrial permeability transition pore (MPTP), depolarization of the inner mitochondrial membrane, and decrease of ATP production. Our work aimed to monitor age-related changes in the Ca2+ ion effect on MPTP and the ability of isolated rat liver mitochondria to accumulate calcium. The mitochondrial calcium retention capacity (CRC) was found to be significantly affected by the age of rats. Measurement of CRC values of the rat liver mitochondria showed two periods when 3 to 17-week old rats were tested. 3-week and 17-week old rats showed lower CRC values than 7-week old animals. Similar changes were observed while testing calcium-induced swelling of rat liver mitochondria. These findings indicate that the mitochondrial energy production system is more resistant to calcium-induced MPTP opening accompanied by the damaging effect of ROS in adult rats than in young and aged animals.
In mammals, the conserved telomere binding protein Rap1 serves a diverse set of nontelomeric functions, including activation of the NF-kB signaling pathway, maintenance of metabolic function in vivo, and transcriptional regulation. Here, we uncover the mechanism by which Rap1 modulates gene expression. Using a separation-of-function allele, we show that Rap1 transcriptional regulation is largely independent of TRF2-mediated binding to telomeres and does not involve direct binding to genomic loci. Instead, Rap1 interacts with the TIP60/p400 complex and modulates its histone acetyltransferase activity. Notably, we show that deletion of Rap1 in mouse embryonic stem cells increases the fraction of two-cell-like cells. Specifically, Rap1 enhances the repressive activity of Tip60/p400 across a subset of two-cell-stage genes, including Zscan4 and the endogenous retrovirus MERVL. Preferential up-regulation of genes proximal to MERVL elements in Rap1-deficient settings implicates these endogenous retroviral elements in the derepression of proximal genes. Altogether, our study reveals an unprecedented link between Rap1 and the TIP60/p400 complex in the regulation of pluripotency.
- MeSH
- genom MeSH
- myší embryonální kmenové buňky metabolismus MeSH
- myši MeSH
- proteiny vázající telomery * genetika metabolismus MeSH
- regulace genové exprese MeSH
- savci genetika MeSH
- telomery * metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
The mitochondrial permeability transition pore (MPTP) is a calcium-dependent, ion non-selective membrane pore with a wide range of functions. Although the MPTP has been studied for more than 50 years, its molecular structure remains unclear. Short-term (reversible) opening of the MPTP protects cells from oxidative damage and enables the efflux of Ca2+ ions from the mitochondrial matrix and cell signaling. However, long-term (irreversible) opening induces processes leading to cell death. Ca2+ ions, reactive oxygen species, and changes in mitochondrial membrane potential regulate pore opening. The sensitivity of the pore to Ca2+ ions changes as an organism ages, and MPTP opening plays a key role in the pathogenesis of many diseases. Most studies of the MPTP have focused on elucidating its molecular structure. However, understanding the mechanisms that will inhibit the MPTP may improve the treatment of diseases associated with its opening. To evaluate the functional state of the MPTP and its inhibitors, it is therefore necessary to use appropriate methods that provide reproducible results across laboratories. This review summarizes our current knowledge of the function and regulation of the MPTP. The latter part of the review introduces two optimized methods for evaluating the functional state of the pore under standardized conditions.
Binary and ternary amorphous transition metal (TM) nitrides and oxides are of great interest because of their suitability for diverse applications ranging from high-temperature machining to the production of optical filters or electrochromic devices. However, understanding of bonding in, and electronic structure of, these materials represents a challenge mainly due to the d electrons in their valence band. In the present work, we report ab initio calculations of the structure and electronic structure of ZrSiN materials. We focus on the methodology needed for the interpretation and automatic analysis of the bonding structure, on the effect of the length of the calculation on the convergence of individual quantities of interest and on the electronic structure of materials. We show that the traditional form of the Wannier function center-based algorithm fails due to the presence of d electrons in the valence band. We propose a modified algorithm, which allows one to analyze bonding structure in TM-based systems. We observe an appearance of valence p states of TM atoms in the electronic spectra of such systems (not only ZrSiN but also NbO(x) and WAuO), and examine the importance of the p states for the character of the bonding as well as for facilitating the bonding analysis. The results show both the physical phenomena and the computational methodology valid for a wide range of TM-based ceramics.
Cystic fibrosis (CF) is a monogenetic disease resulting from mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene encoding an anion channel. Recent evidence indicates that CFTR plays a role in other cellular processes, namely in development, cellular differentiation and wound healing. Accordingly, CFTR has been proposed to function as a tumour suppressor in a wide range of cancers. Along these lines, CF was recently suggested to be associated with epithelial-mesenchymal transition (EMT), a latent developmental process, which can be re-activated in fibrosis and cancer. However, it is unknown whether EMT is indeed active in CF and if EMT is triggered by dysfunctional CFTR itself or a consequence of secondary complications of CF. In this study, we investigated the occurrence of EMT in airways native tissue, primary cells and cell lines expressing mutant CFTR through the expression of epithelial and mesenchymal markers as well as EMT-associated transcription factors. Transepithelial electrical resistance, proliferation and regeneration rates, and cell resistance to TGF-β1induced EMT were also measured. CF tissues/cells expressing mutant CFTR displayed several signs of active EMT, namely: destructured epithelial proteins, defective cell junctions, increased levels of mesenchymal markers and EMT-associated transcription factors, hyper-proliferation and impaired wound healing. Importantly, we found evidence that the mutant CFTR triggered EMT was mediated by EMT-associated transcription factor TWIST1. Further, our data show that CF cells are over-sensitive to EMT but the CF EMT phenotype can be reversed by CFTR modulator drugs. Altogether, these results identify for the first time that EMT is intrinsically triggered by the absence of functional CFTR through a TWIST1 dependent mechanism and indicate that CFTR plays a direct role in EMT protection. This mechanistic link is a plausible explanation for the high incidence of fibrosis and cancer in CF, as well as for the role of CFTR as tumour suppressor protein.
- MeSH
- cystická fibróza metabolismus patologie MeSH
- epitelo-mezenchymální tranzice MeSH
- HEK293 buňky MeSH
- jaderné proteiny metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- onkogeny genetika MeSH
- protein CFTR metabolismus MeSH
- transkripční faktor Twist metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole-CypD complex is more stable than cyclosporin A (CsA)-CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings.Communicated by Ramaswamy H. Sarma.
- MeSH
- adenosintrifosfát metabolismus MeSH
- anastrozol farmakologie metabolismus MeSH
- cyklofiliny genetika metabolismus MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé MeSH
- mitochondriální nemoci * metabolismus MeSH
- mitochondrie metabolismus MeSH
- peptidylprolylisomerasa F MeSH
- přechodový pór mitochondriální permeability * metabolismus farmakologie MeSH
- transportní proteiny mitochondriální membrány metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
