Alzheimer's disease (AD) is characterised by the accumulation of intracytoplasmic aggregates of tau protein, which are suggested to spread in a prion-like manner between interconnected brain regions. This spreading is mediated by the secretion and uptake of tau from the extracellular space or direct cell-to-cell transmission through cellular protrusions. The prion-like tau then converts the endogenous, normal tau into pathological forms, resulting in neurodegeneration. The endoplasmic reticulum/Golgi-independent tau secretion through unconventional secretory pathways involves delivering misfolded and aggregated tau to the plasma membrane and its release into the extracellular space by non-vesicular and vesicular mechanisms. Although cytoplasmic tau was thought to be released only from degenerating cells, studies now show that cells constitutively secrete tau at low levels under physiological conditions. The mechanisms of secretion of tau under physiological and pathological conditions remain unclear. Therefore, a better understanding of these pathways is essential for developing therapeutic approaches that can target prion-like tau forms to prevent neurodegeneration progression in AD. This review focuses on unconventional secretion pathways involved in the spread of tau pathology in AD and presents these pathways as prospective areas for future AD drug discovery and development.
- MeSH
- Alzheimerova nemoc metabolismus patologie MeSH
- lidé MeSH
- mezibuněčná komunikace fyziologie MeSH
- mozek metabolismus patologie MeSH
- patologická konformace proteinů metabolismus patologie MeSH
- proteiny tau metabolismus MeSH
- tauopatie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
MiR-126 has been shown to suppress malignant mesothelioma (MM) by targeting cancer-related genes without inducing toxicity or histopathological changes. Exosomes provide the opportunity to deliver therapeutic cargo to cancer stroma. Here, a tumour stromal model composed of endothelial cells (HUVECs), fibroblasts (IMR-90 cells), non-malignant mesothelial cells (Met-5A cells) and MM cells (H28 and MM-B1 cells) was used. The cells were treated with exosomes from HUVECs carrying endogenous (exo-HUVEC) and enriched miR-126 (exo-HUVECmiR-126), and the uptake/turnover of exosomes; miR-126 distribution within the stroma; and effect of miR-126 on cell signalling, angiogenesis and cell proliferation were evaluated. Based on the sensitivity of MM cells to exo-HUVEC miR-126 treatment, miR-126 was distributed differently across stromal cells. The reduced miR-126 content in fibroblasts in favour of endothelial cells reduced angiogenesis and suppressed cell growth in an miR-126-sensitive environment. Conversely, the accumulation of miR-126 in fibroblasts and the reduced level of miR-126 in endothelial cells induced tube formation in an miR-126-resistant environment via VEGF/EGFL7 upregulation and IRS1-mediated cell proliferation. These findings suggest that transfer of miR-126 via HUVEC-derived exosomes represents a novel strategy to inhibit angiogenesis and cell growth in MM.
- MeSH
- epidermální růstové faktory metabolismus MeSH
- exozómy metabolismus MeSH
- fibroblasty metabolismus MeSH
- karcinogeneze metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mezibuněčná komunikace fyziologie MeSH
- mezoteliom metabolismus MeSH
- mikro RNA metabolismus MeSH
- nádory plic metabolismus MeSH
- proteiny vázající vápník metabolismus MeSH
- signální transdukce fyziologie MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Yeast biofilms are complex multicellular structures, in which the cells are well protected against drugs and other treatments and thus highly resistant to antifungal therapies. Colony biofilms represent an ideal system for studying molecular mechanisms and regulations involved in development and internal organization of biofilm structure as well as those that are involved in fungal domestication. We have identified here antagonistic functional interactions between transcriptional regulators Cyc8p and Tup1p that modulate the life-style of natural S. cerevisiae strains between biofilm and domesticated mode. Herein, strains with different levels of Cyc8p and Tup1p regulators were constructed, analyzed for processes involved in colony biofilm development and used in the identification of modes of regulation of Flo11p, a key adhesin in biofilm formation. Our data show that Tup1p and Cyc8p regulate biofilm formation in the opposite manner, being positive and negative regulators of colony complexity, cell-cell interaction and adhesion to surfaces. Notably, in-depth analysis of regulation of expression of Flo11p adhesin revealed that Cyc8p itself is the key repressor of FLO11 expression, whereas Tup1p counteracts Cyc8p's repressive function and, in addition, counters Flo11p degradation by an extracellular protease. Interestingly, the opposing actions of Tup1p and Cyc8p concern processes crucial to the biofilm mode of yeast multicellularity, whereas other multicellular processes such as cell flocculation are co-repressed by both regulators. This study provides insight into the mechanisms regulating complexity of the biofilm lifestyle of yeast grown on semisolid surfaces.
- MeSH
- biofilmy * MeSH
- buněčná adheze fyziologie MeSH
- jaderné proteiny genetika metabolismus MeSH
- membránové glykoproteiny genetika metabolismus MeSH
- mezibuněčná komunikace fyziologie MeSH
- regulace genové exprese u hub * MeSH
- represorové proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Contents 516 I. 516 II. 518 III. 518 IV. 521 V. 523 VI. 523 VII. 526 526 References 526 SUMMARY: The relevance of infochemicals in the relationships between organisms is emerging as a fundamental aspect of aquatic ecology. Exchanges of chemical cues are likely to occur not only between organisms of different species, but also between conspecific individuals. Especially intriguing is the investigation of chemical communication in microalgae, because of the relevance of these organisms for global primary production and their key role in trophic webs. Intraspecific communication between algae has been investigated mostly in relation to sexuality and mating. The literature also contains information on other types of intraspecific chemical communication that have not always been explicitly tagged as ways to communicate to conspecifics. However, the proposed role of certain compounds as intraspecific infochemicals appears questionable. In this article, we make use of this plethora of information to describe the various instances of intraspecific chemical communication between conspecific microalgae and to identify the common traits and ecological significance of intraspecific communication. We also discuss the evolutionary implications of intraspecific chemical communication and the mechanisms by which it can be inherited. A special focus is the genetic diversity among conspecific algae, including the possibility that genetic diversity is an absolute requirement for intraspecific chemical communication.
Intracellular and extracellular mechanical forces play a crucial role during tissue growth, modulating nuclear shape and function and resulting in complex collective cell behaviour. However, the mechanistic understanding of how the orientation, shape, symmetry and homogeneity of cells are affected by environmental geometry is still lacking. Here we investigate cooperative cell behaviour and patterns under geometric constraints created by topographically patterned substrates. We show how cells cooperatively adopt their geometry, shape, positioning of the nucleus and subsequent proliferation activity. Our findings indicate that geometric constraints induce significant squeezing of cells and nuclei, cytoskeleton reorganization, drastic condensation of chromatin resulting in a change in the cell proliferation rate and the anisotropic growth of cultures. Altogether, this work not only demonstrates complex non-trivial collective cellular responses to geometrical constraints but also provides a tentative explanation of the observed cell culture patterns grown on different topographically patterned substrates. These findings provide important fundamental knowledge, which could serve as a basis for better controlled tissue growth and cell-engineering applications.
- MeSH
- biologické modely * MeSH
- buněčné jádro fyziologie ultrastruktura MeSH
- buněčný převod mechanických signálů fyziologie MeSH
- buňky Hep G2 MeSH
- lidé MeSH
- mezibuněčná komunikace fyziologie MeSH
- počítačová simulace MeSH
- proliferace buněk fyziologie MeSH
- velikost buňky * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Intercellular interactions are able to influence the biological properties of many types of tumors including malignant melanoma. Differentiation pattern of melanoma cells is significantly influenced by the melanoma-associated fibroblasts but the information about interaction of these cells with other important element of melanoma microenvironment, resp. with keratinocytes, is limited. In this, study we tested the effect of fibroblasts isolated from malignant melanoma on phenotype of normal human keratinocytes, especially on their expression of vimentin, a cytoskeletal protein weakly expressed in normal human keratinocytes. The co-culture with normal dermal fibroblasts was used for comparison. The results demonstrated the high expression of vimentin in keratinocytes co-cultured with melanoma-associated fibroblasts compared with those co-cultured with normal dermal fibroblasts. These data suggest participation of melanoma-associated fibroblasts-keratinocyte crosstalk in formation of melanoma niche.
- MeSH
- biomedicínský výzkum metody MeSH
- fenotyp MeSH
- fibroblasty * cytologie mikrobiologie patologie MeSH
- imunohistochemie metody využití MeSH
- interakce genů a prostředí MeSH
- keratinocyty * cytologie enzymologie imunologie MeSH
- kultivační techniky metody využití MeSH
- lidé MeSH
- melanom * genetika imunologie mikrobiologie MeSH
- mezibuněčná komunikace fyziologie genetika imunologie MeSH
- nádorové buňky kultivované cytologie imunologie metabolismus MeSH
- statistika jako téma MeSH
- vimentin imunologie izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
INTRODUCTION: The unique pulp-dentin complex demonstrates strong regenerative potential, which enables it to respond to disease and traumatic injury. Identifying the proteins of the pulp-dentin complex is crucial to understanding the mechanisms of regeneration, tissue calcification, defense processes, and the reparation of dentin by dental pulp. The lack of knowledge of these proteins limits the development of more efficient therapies. METHODS: The proteomic profile of human tooth pulp was investigated and compared with the proteome of human dentin and blood. The samples of tooth pulp were obtained from 5 sound permanent human third molars of 5 adults (n = 5). The extracted proteins were separated by 2-dimensional gel electrophoresis, analyzed by nano-liquid chromatography tandem mass spectrometry, and identified by correlating mass spectra to the proteomic databases. RESULTS: A total of 342 proteins were identified with high confidence, and 2 proteins were detected for the first time in an actual human sample. The identified tooth pulp proteins have a variety of functions: structural, catalytic, transporter, protease activity, immune response, and many others. In a comparison with dentin and blood plasma, 140 (pulp/dentin) shared proteins were identified, 37 of which were not observed in plasma. It can be suggested that they might participate in the unique pulp-dentin complex. CONCLUSIONS: This proteomic investigation of human tooth pulp, together with the previously published study of human dentin, is one of the most comprehensive proteome lists of human teeth to date.
- MeSH
- 2D gelová elektroforéza MeSH
- chromatografie kapalinová MeSH
- dentin chemie MeSH
- dospělí MeSH
- energetický metabolismus fyziologie MeSH
- hmotnostní spektrometrie MeSH
- imunoproteiny analýza MeSH
- krevní proteiny analýza MeSH
- lidé MeSH
- mezibuněčná komunikace fyziologie MeSH
- mladý dospělý MeSH
- nanotechnologie MeSH
- proliferace buněk MeSH
- proteiny metabolismus MeSH
- proteom analýza klasifikace MeSH
- signální transdukce fyziologie MeSH
- tandemová hmotnostní spektrometrie MeSH
- zubní dřeň chemie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Volume transmission is a form of intercellular communication that does not require synapses; it is based on the diffusion of neuroactive substances across the brain extracellular space (ECS) and their binding to extrasynaptic high-affinity receptors on neurons or glia. Extracellular diffusion is restricted by the limited volume of the ECS, which is described by the ECS volume fraction α, and the presence of diffusion barriers, reflected by tortuosity λ, that are created, for example, by fine astrocytic processes or extracellular matrix (ECM) molecules. Organized astrocytic processes, ECM scaffolds or myelin sheets channel the extracellular diffusion so that it is facilitated in a certain direction, i.e. anisotropic. The diffusion properties of the ECS are profoundly influenced by various processes such as the swelling and morphological rebuilding of astrocytes during either transient or persisting physiological or pathological states, or the remodelling of the ECM in tumorous or epileptogenic tissue, during Alzheimer's disease, after enzymatic treatment or in transgenic animals. The changing diffusion properties of the ECM influence neuron-glia interaction, learning abilities, the extent of neuronal damage and even cell migration. From a clinical point of view, diffusion parameter changes occurring during pathological states could be important for diagnosis, drug delivery and treatment.
- MeSH
- anizotropie MeSH
- astrocyty patologie MeSH
- difuze MeSH
- extracelulární matrix fyziologie MeSH
- lidé MeSH
- mezibuněčná komunikace fyziologie MeSH
- nervový přenos fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
