33094622 OR Insights into the physiology of C-peptide Dotaz Zobrazit nápovědu
Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue.
- MeSH
- C-peptid aplikace a dávkování fyziologie MeSH
- diabetes mellitus 2. typu komplikace farmakoterapie patologie MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- nemoci cév etiologie metabolismus patologie prevence a kontrola MeSH
- nemoci nervového systému etiologie metabolismus patologie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Prominin-1 (CD133) is physiologically expressed at the apical membranes of secretory (serous and mucous) and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133) applied on paraffin-embedded sections and characterized its occurrence in saliva. The 80B258 epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid carcinoma. The 80B258 immunoreactivity was predominately detected at the apical membrane of tumor cells showing acinar or intercalated duct cell differentiation, which lined duct- or cyst-like structures, and in luminal secretions. It was observed on the whole cell membrane in non-luminal structures present in the vicinity of thin-walled blood vessels and hemorrhagic areas in adenoid cystic carcinoma. Of note, AC133 labeled only a subset of 80B258-positive structures. In peritumoral salivary gland tissues as well as in obstructive sialadenitis, an up-regulation of prominin-1 (both 80B258 and AC133 immunoreactivities) was observed in intercalated duct cells. In most tissues, prominin-1 was partially co-expressed with two cancer markers: carcinoembryonic antigen (CEA) and mucin-1 (MUC1). Differential centrifugation of saliva followed by immunoblotting indicated that all three markers were released in association with small membrane vesicles. Immuno-isolated prominin-1-positive vesicles contained CEA and MUC1, but also exosome-related proteins CD63, flotillin-1, flotillin-2 and the adaptor protein syntenin-1. The latter protein was shown to interact with prominin-1 as demonstrated by its co-immunoisolation. A fraction of saliva-associated prominin-1 appeared to be ubiquitinated. Collectively, our findings bring new insights into the biochemistry and trafficking of prominin-1 as well as its immunohistochemical profile in certain types of salivary gland tumors and inflammatory diseases.
- MeSH
- buněčná membrána metabolismus MeSH
- CD antigeny metabolismus MeSH
- glykoproteiny metabolismus sekrece MeSH
- karcinoembryonální antigen metabolismus MeSH
- lidé MeSH
- mucin 1 metabolismus MeSH
- nádory slinných žláz metabolismus patologie MeSH
- peptidy metabolismus sekrece MeSH
- regulace genové exprese u nádorů MeSH
- sialoadenitida metabolismus patologie MeSH
- sliny metabolismus MeSH
- stupeň nádoru MeSH
- synteniny metabolismus MeSH
- ubikvitinace * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In nature, root systems of most terrestrial plants are protected from light exposure by growing in a dark soil environment. Hence, in vitro cultivation in transparent Petri dishes leads to physiological perturbations, but the mechanisms underlying root-mediated light perception and responses have not been fully elucidated. Thus, we compared Arabidopsis thaliana seedling development in transparent and darkened Petri dishes at low light intensity (20 µmol m(-2) s(-1)), allowing us to follow (inter alia) hypocotyl elongation, which is an excellent process for studying interactions of signals involved in the regulation of growth and developmental responses. To obtain insights into molecular events underlying differences in seedling growth under these two conditions, we employed liquid chromatography-mass spectrometry (LC-MS) shotgun proteomics (available via the PRIDE deposit PXD001612). In total, we quantified the relative abundances of peptides representing 1,209 proteins detected in all sample replicates of LC-MS analyses. Comparison of MS spectra after manual validation revealed 48 differentially expressed proteins. Functional classification, analysis of available gene expression data and literature searches revealed alterations associated with root illumination (inter alia) in autotrophic CO2 fixation, C compound and carbohydrate metabolism, and nitrogen metabolism. The results also indicate a previously unreported role for cytokinin plant hormones in the escape-tropism response to root illumination. We complemented these results with reverse transcription followed by quantitative PCR (RT-qPCR), chlorophyll fluorescence and detailed cytokinin signaling analyses, detecting in the latter a significant increase in the activity of the cytokinin two-component signaling cascade in roots and implicating the cytokinin receptor AHK3 as the major mediator of root to hypocotyl signaling in responses to root illumination.
- MeSH
- aktiny metabolismus MeSH
- Arabidopsis metabolismus účinky záření MeSH
- chromatografie kapalinová MeSH
- cytokininy metabolismus MeSH
- down regulace účinky záření MeSH
- fotosyntéza účinky záření MeSH
- hmotnostní spektrometrie MeSH
- hypokotyl anatomie a histologie účinky záření MeSH
- kořeny rostlin anatomie a histologie účinky záření MeSH
- proteom metabolismus MeSH
- proteomika MeSH
- rostlinné proteiny metabolismus MeSH
- signální transdukce * účinky záření MeSH
- světlo MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
To achieve host colonization, successful pathogens need to overcome plant basal defences. For this, (hemi)biotrophic pathogens secrete effectors that interfere with a range of physiological processes of the host plant. AvrLm4-7 is one of the cloned effectors from the hemibiotrophic fungus Leptosphaeria maculans 'brassicaceae' infecting mainly oilseed rape (Brassica napus). Although its mode of action is still unknown, AvrLm4-7 is strongly involved in L. maculans virulence. Here, we investigated the effect of AvrLm4-7 on plant defence responses in a susceptible cultivar of B. napus. Using two isogenic L. maculans isolates differing in the presence of a functional AvrLm4-7 allele [absence ('a4a7') and presence ('A4A7') of the allele], the plant hormone concentrations, defence-related gene transcription and reactive oxygen species (ROS) accumulation were analysed in infected B. napus cotyledons. Various components of the plant immune system were affected. Infection with the 'A4A7' isolate caused suppression of salicylic acid- and ethylene-dependent signalling, the pathways regulating an effective defence against L. maculans infection. Furthermore, ROS accumulation was decreased in cotyledons infected with the 'A4A7' isolate. Treatment with an antioxidant agent, ascorbic acid, increased the aggressiveness of the 'a4a7' L. maculans isolate, but not that of the 'A4A7' isolate. Together, our results suggest that the increased aggressiveness of the 'A4A7' L. maculans isolate could be caused by defects in ROS-dependent defence and/or linked to suppressed SA and ET signalling. This is the first study to provide insights into the manipulation of B. napus defence responses by an effector of L. maculans.
- MeSH
- alely MeSH
- antioxidancia farmakologie MeSH
- Ascomycota účinky léků izolace a purifikace metabolismus MeSH
- Brassica napus účinky léků růst a vývoj metabolismus mikrobiologie MeSH
- chromatografie kapalinová MeSH
- cyklopentany metabolismus MeSH
- ethyleny metabolismus MeSH
- fungální proteiny metabolismus MeSH
- hmotnostní spektrometrie MeSH
- interakce hostitele a patogenu účinky léků MeSH
- kotyledon účinky léků metabolismus mikrobiologie MeSH
- kyselina abscisová metabolismus MeSH
- kyselina askorbová farmakologie MeSH
- kyselina salicylová metabolismus MeSH
- oxylipiny metabolismus MeSH
- peroxid vodíku metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- regulátory růstu rostlin metabolismus MeSH
- signální transdukce * účinky léků MeSH
- Publikační typ
- časopisecké články MeSH