Protease-activated receptors (PARs) are transmembrane proteins which rank among G-protein-coupled receptors. So far, four PARs (PAR1-4) have been described. They are activated by a protease cleavage at the N-terminal part of the receptor. Through the cleavage a new N-terminus appears which acts as a ligand activating the receptor. A peptide of the same amino acid sequence as the new N-terminus can activate the receptor without its cleavage. Some non-specific proteases can cleave PAR receptors at different sites, which results in changes in cell signaling. Higher activities of PARs have been observed under various pathological conditions, such as thrombosis, atherosclerosis, inflammations or neurodegeneration. Specific modulators of PAR signaling are a promising class of compounds with a wide therapeutic potential. First PAR inhibitors were based mainly on the amino acid sequence in the activating peptides. Recently, new, low-molecularweight, very specific and effective inhibitors have been developed. One of them, vorapaxar, passed the clinical tests and was introduced to the market.
- MeSH
- kardiovaskulární nemoci farmakoterapie MeSH
- kinasa 1 receptorů spřažených s G-proteiny * MeSH
- lidé MeSH
- neurodegenerativní nemoci farmakoterapie MeSH
- peptidy MeSH
- receptor PAR-1 * antagonisté a inhibitory MeSH
- receptory thrombinu * antagonisté a inhibitory MeSH
- thrombin MeSH
- trypsin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Buněčný prionový protein (PrPC) je známý především jako prekurzor patologické konformační izoformy prionového proteinu PrPTSE, jejíž hromadění v mozku je spojeno s patogenezí prionových onemocnění. Výsledky četných studií naznačují, že PrPC má také řadu fyziologických funkcí a účastní se mnoha buněčných procesů; přesvědčivé důkazy nicméně stále chybí. Popsána byla možná úloha PrPC v regulaci apoptózy, ochraně proti oxidačnímu stresu, buněčné adhezi nebo procesech učení a paměti. PrPC zřejmě významně ovlivňuje také diferenciaci a proliferační aktivitu buněk. Během embryonálního vývoje má hladina exprese PrPC vliv na transkripci genů, které se podílejí na regulaci pluripotence kmenových buněk v raných fázích diferenciace. Důležitou roli hraje PrPC v nervové soustavě, kde se uplatňuje ve vývoji a zrání neuronů a při formování neuronálních obvodů. V neposlední řadě se PrPC zřejmě může podílet i na diferenciaci a proliferaci tkáňově specifických kmenových buněk, jako jsou neuronální, myogenní nebo hematopoietické prekurzory.
The cellular prion protein (PrPC) is well-known for its ability to converse into its pathological isoform, PrPTSE. Accumulation of PrPTSE in the brain is associated with pathogenesis of prion diseases. Numerous studies have suggested that PrPC has a number of physiological functions and participates in many cellular processes. However, convincing evidence is still missing. Possible functions of PrPC include a role in regulation of apoptosis, protection against oxidative stress, cell adhesion or processes of learning and memory. This protein also seems to influence cell proliferation and differentiation. The level of PrPC expression during embryonic development affects transcription of genes encoding factors involved in the regulation of stem cells pluripotency at early stages of differentiation. In the nervous system, PrPC plays an important role in neuronal development, maturation and neural circuit formation. Finally, PrPC can probably also participate in the differentiation and proliferation of tissue-specific stem cells such as neuronal, hematopoietic or myogenic precursors. Key words: prions – prion protein – PrPC – cell differentiation – cell proliferation – embryonic stem cells – neurons – neurogenesis The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
- MeSH
- buněčná diferenciace MeSH
- embryonální kmenové buňky MeSH
- lidé MeSH
- neurogeneze * MeSH
- prionové nemoci * etiologie MeSH
- priony * fyziologie genetika MeSH
- proliferace buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Radix lagotis is an intermediate snail host of the nasal bird schistosome Trichobilharzia regenti. Changes in defence responses in infected snails that might be related to host-parasite compatibility are not known. This study therefore aimed to characterize R. lagotis haemocyte defence mechanisms and determine the extent to which they are modulated by T. regenti. Histological observations of R. lagotis infected with T. regenti revealed that early phases of infection were accompanied by haemocyte accumulation around the developing larvae 2-36 h post exposure (p.e.) to the parasite. At later time points, 44-92 h p.e., no haemocytes were observed around T. regenti. Additionally, microtubular aggregates likely corresponding to phagocytosed ciliary plates of T. regenti miracidia were observed within haemocytes by use of transmission electron microscopy. When the infection was in the patent phase, haemocyte phagocytic activity and hydrogen peroxide production were significantly reduced in infected R. lagotis when compared to uninfected counterparts, whereas haemocyte abundance increased in infected snails. At a molecular level, protein kinase C (PKC) and extracellular-signal regulated kinase (ERK) were found to play an important role in regulating these defence reactions in R. lagotis. Moreover, haemocytes from snails with patent infection displayed lower PKC and ERK activity in cell adhesion assays when compared to those from uninfected snails, which may therefore be related to the reduced defence activities of these cells. These data provide the first integrated insight into the immunobiology of R. lagotis and demonstrate modulation of haemocyte-mediated responses in patent T. regenti infected snails. Given that immunomodulation occurs during patency, interference of snail-host defence by T. regenti might be important for the sustained production and/or release of infective cercariae.
- MeSH
- extracelulárním signálem regulované MAP kinasy metabolismus MeSH
- fagocytóza imunologie MeSH
- hemocyty imunologie metabolismus parazitologie MeSH
- interakce hostitele a parazita imunologie MeSH
- Lymnaea imunologie metabolismus parazitologie MeSH
- peroxid vodíku metabolismus MeSH
- proteinkinasa C metabolismus MeSH
- Schistosomatidae * ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
