• MeSH
• imunochemie MeSH
• krysa rodu rattus MeSH
• neurotrofní faktory analýza   sekrece   MeSH
• novorozená zvířata MeSH
• peptid spojený s genem pro kalcitonin analýza   sekrece   MeSH
• srdeční síně cytologie   inervace   MeSH
• synaptické vezikuly sekrece   MeSH
• vývojová biologie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

We hypothesized that hypertension-related myocardial remodeling characterized by hypertrophy and fibrosis might be accompanied by cell-to-cell gap junction alterations that may account for increased arrhythmogenesis. Intercellular junctions and expression of gap junction protein connexin-43 were analyzed in rat heart tissues from both spontaneous (SHR) and L-NAME model of hypertension. Isolated heart preparation was used to examine susceptibility of the heart to lethal ventricular fibrillation induced by low potassium perfusion. Ultrastructure observation revealed enhanced neoformation of side-to-side type while internalization of end-to-end type (intercalated disc-related) of gap junctions prevailed in the myocardium of rats suffering from either spontaneous or L-NAME-induced hypertension. In parallel, immunolabeling showed increased number of connexin-43 positive gap junctions in lateral cell membrane surfaces, particularly in SHR. Besides, focal loss of immunopositive signal was observed more frequently in hearts of rats treated with L-NAME. There was a significantly higher incidence of hypokalemia-induced ventricular fibrillation in hypertensive compared to normotensive rat hearts. We conclude that adaptation of the heart to hypertension-induced mechanical overload results in maladaptive gap junction remodeling that consequently promotes development of fatal arrhythmias.

• MeSH
• draslík MeSH
• fibrilace komor chemicky indukované   metabolismus   MeSH
• fyziologická adaptace MeSH
• hypertenze metabolismus   patologie   MeSH
• hypokalemie metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• krysa rodu rattus MeSH
• mezerový spoj metabolismus   MeSH
• myokard metabolismus   ultrastruktura   MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• srdeční komory mikrobiologie   virologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• Charcotova-Marieova-Toothova nemoc genetika   klasifikace   patologie   MeSH
• diferenciální diagnóza MeSH
• konexiny MeSH
• lidé MeSH
• protein GAP-43 MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter - intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9±12.8; range 30-74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8±8.5; range 45-70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; p<0.001). The proportion of GAP-43 immunoreactive intraepidermal nerve fibers was significantly lower in DM2 patients compared to healthy controls (73.6% of 337 PGP 9.5 positive fibers; p<0.001); ranged from 0 to 98.1%. In conclusion, these results show that impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43, might be a marker of incipient diabetic neuropathy.

• MeSH
• diabetes mellitus 2. typu genetika   metabolismus   patofyziologie   MeSH
• diabetické neuropatie genetika   metabolismus   patofyziologie   MeSH
• dospělí MeSH
• kůže inervace   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervová vlákna nemyelinizovaná patologie   fyziologie   MeSH
• nervová vlákna fyziologie   MeSH
• pilotní projekty MeSH
• protein GAP-43 biosyntéza   genetika   MeSH
• regenerace nervu genetika   MeSH
• regulace genové exprese MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Although most heterotrimeric G proteins are thought to dissociate into Gα and Gβγ subunits upon activation, the evidence in the Gi/o family has long been inconsistent and contradictory. The Gi/o protein family mediates inhibition of cAMP production and regulates the activity of ion channels. On the basis of experimental evidence, both heterotrimer dissociation and rearrangement have been postulated as crucial steps of Gi/o protein activation and signal transduction. We have now investigated the process of Gi/o activation in living cells directly by two-photon polarization microscopy and indirectly by observations of G protein-coupled receptor kinase-derived polypeptides. Our observations of existing fluorescently labeled and non-modified Gαi/o constructs indicate that the molecular mechanism of Gαi/o activation is affected by the presence and localization of the fluorescent label. All investigated non-labeled, non-modified Gi/o complexes dissociate extensively upon activation. The dissociated subunits can activate downstream effectors and are thus likely to be the major activated Gi/o form. Constructs of Gαi/o subunits fluorescently labeled at the N terminus (GAP43-CFP-Gαi/o) seem to faithfully reproduce the behavior of the non-modified Gαi/o subunits. Gαi constructs labeled within the helical domain (Gαi-L91-YFP) largely do not dissociate upon activation, yet still activate downstream effectors, suggesting that the dissociation seen in non-modified Gαi/o proteins is not required for downstream signaling. Our results appear to reconcile disparate published data and settle a long running dispute.

• MeSH
• aktivace enzymů fyziologie   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• protein GAP-43 genetika   metabolismus   MeSH
• proteiny vázající GTP - alfa-podjednotky Gi-Go genetika   metabolismus   MeSH
• proteiny vázající GTP - beta-podjednotky genetika   metabolismus   MeSH
• proteiny vázající GTP - gama-podjednotky genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• axony fyziologie   MeSH
• krysa rodu rattus MeSH
• membránové glykoproteiny biosyntéza   MeSH
• nervus ischiadicus fyziologie   MeSH
• proteiny nervové tkáně biosyntéza   MeSH
• regenerace nervu MeSH
• Schwannovy buňky fyziologie   MeSH
• stárnutí MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• bulbus olfactorius patologie   MeSH
• krysa rodu rattus MeSH
• neurony MeSH
• proteiny nervové tkáně MeSH
• regenerace nervu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

Peripheral nerve injury results in profound alterations of the affected neurons resulting from the interplay between intrinsic and extrinsic molecular events. Restarting the neuronal regenerative program is an important prerequisite for functional recovery of the injured peripheral nerve. The primary sensory neurons with their cell bodies in the dorsal root ganglia provide a useful in vivo and in vitro model for studying the mechanisms that regulate intrinsic neuronal regeneration capacity following axotomy. These studies frequently need to indicate the regenerative status of the corresponding neurons. We summarize the critical issues regarding immunohistochemical detection of several regeneration-associated proteins as markers for the initiation of the regeneration program in rat primary sensory neurons and indicators of axon regeneration in the peripheral nerves. This overview also includes our own results of GAP43 and SCG10 expression in different DRG neurons following double immunostaining with molecular markers of neuronal subpopulations (NF200, CGRP, and IB4) as well as transcription factors (ATF3 and activated STAT3) following unilateral sciatic nerve injury. Anat Rec, 301:1618-1627, 2018. © 2018 Wiley Periodicals, Inc.

• MeSH
• axony metabolismus   MeSH
• biologické markery metabolismus   MeSH
• fyziologický stres MeSH
• korneocytární obal - proteiny bohaté na prolin metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• mikrotubulární proteiny MeSH
• nervové receptory klasifikace   fyziologie   MeSH
• protein GAP-43 metabolismus   MeSH
• regenerace nervu * MeSH
• spinální ganglia cytologie   metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNFα, IL-4, IL-1β, IL-2, IL-6 and IL-12 and increased the levels of MIP-1α and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application.

• MeSH
• chemokin CCL5 genetika   metabolismus   MeSH
• fibroblastový růstový faktor 2 genetika   metabolismus   MeSH
• gliový fibrilární kyselý protein genetika   metabolismus   MeSH
• interferonové regulační faktory genetika   metabolismus   MeSH
• interleukiny genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• lokomoce MeSH
• mezenchymální kmenové buňky metabolismus   MeSH
• poranění míchy metabolismus   terapie   MeSH
• potkani Wistar MeSH
• protein GAP-43 genetika   metabolismus   MeSH
• receptory imunologické genetika   metabolismus   MeSH
• TNF-alfa genetika   metabolismus   MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH