- Publikační typ
- abstrakt z konference MeSH
(Pro)renin receptor (PRR) contributes to regulating many physiological and pathological processes; however, the role of PRR-mediated signaling pathways in myocardial ischemia/reperfusion injury (IRI) remains unclear. In this study, we used an in vitro model of hypoxia/reoxygenation (H/R) to mimic IRI and carried out PRR knockdown by siRNA and PRR overexpression using cDNA in H9c2 cells. Cell proliferation activity was examined by MTT and Cell Counting Kit-8 (CCK-8) assays. Apoptosis-related factors, autophagy markers and beta-catenin pathway activity were assessed by real-time PCR and western blotting. After 24 h of hypoxia followed by 2 h of reoxygenation, the expression levels of PRR, LC3B-I/II, Beclin1, cleaved caspase-3, cleaved caspase-9 and Bax were upregulated, suggesting that apoptosis and autophagy were increased in H9c2 cells. Contrary to the effects of PRR downregulation, the overexpression of PRR inhibited proliferation, induced apoptosis, increased the expression of pro-apoptotic factors and autophagy markers, and promoted activation of the beta-catenin pathway. Furthermore, all these effects were reversed by treatment with the beta-catenin antagonist DKK-1. Thus, we concluded that PRR activation can trigger H/R-induced apoptosis and autophagy in H9c2 cells through the beta-catenin signaling pathway, which may provide new therapeutic targets for the prevention and treatment of myocardial IRI.
- MeSH
- apoptóza fyziologie MeSH
- autofagie fyziologie MeSH
- beta-katenin metabolismus MeSH
- buněčné linie MeSH
- hypoxie buňky fyziologie MeSH
- kardiomyocyty metabolismus patologie MeSH
- krysa rodu rattus MeSH
- kyslík metabolismus MeSH
- receptory buněčného povrchu metabolismus MeSH
- reperfuzní poškození myokardu metabolismus patologie MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
A Vero E6 cell culture isolate of Tula virus (TUL), a hantavirus first detected in European common voles (Microtus arvalis and M. rossiaemeridionalis) by RT-PCR was obtained after initial passaging of TUL-infected vole lung samples in laboratory-colonized M. arvalis. TUL was defined as a classical serotype by a cross-focus-reduction neutralization test (FRNT) and was also shown to be distinct from other hantaviruses by haemagglutination inhibition assay. The sequences of S, M and partial L genome segments of the isolate were determined: the S segment was 99.9% identical to the original rodent-derived sequence. Serological evidence for a previous TUL infection was obtained from the serum of a blood donor living near a TUL focus in Moravia, Czech Republic, showing at least a 16-fold higher FRNT titre to TUL as compared to Puumala or other hantaviruses.
- MeSH
- Arvicolinae virologie MeSH
- Cercopithecus aethiops MeSH
- hantavirové infekce imunologie patologie virologie MeSH
- Hantavirus genetika imunologie izolace a purifikace MeSH
- králíci MeSH
- molekulární sekvence - údaje MeSH
- protilátky virové krev MeSH
- RNA virová * analýza MeSH
- sekvence nukleotidů MeSH
- sérotypizace MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Hantavirus carried by the European common vole Microtus arvalis from Moravia (Czech Republic) was analyzed by RT-PCR-sequencing and by reactivity with a panel of monoclonal antibodies (MAbs). Sequencing of the full-length S segment and the proximal part of the M segment showed that the virus belonged to genotype Tula (TUL) we discovered earlier in Microtus arvalis from Central Russia. This finding supported the concept of host dependence of hantaviruses. Phylogenetic analyses suggested a similar evolutionary history for S and M genes of TUL strains; thus far there is no evidence for reassortment in TUL. Geographic clustering of TUL genetic variants was observed and different levels of the genetic variability were revealed resembling those estimated for another hantavirus, Puumala (PUU). Comparison of the deduced N protein sequence from Russia and from Moravia showed that genetic drift in TUL occurred not only by accumulation of point mutations but also by the deletion of a nucleotide triplet. It encoded Ser252 which was located within a highly variable hydrophilic part of the N protein carrying B-cell epitopes and presumably forming a loop. Analysis of naturally expressed TUL N-antigen derived from lung tissue of infected voles with MAbs indicated antigenic heterogeneity among TUL strains.
- MeSH
- antigeny virové imunologie MeSH
- Arvicolinae virologie MeSH
- DNA virů MeSH
- fylogeneze MeSH
- genetická variace MeSH
- Hantavirus klasifikace genetika imunologie MeSH
- králíci MeSH
- molekulární sekvence - údaje MeSH
- monoklonální protilátky imunologie MeSH
- nukleokapsida imunologie MeSH
- protilátky virové imunologie MeSH
- RNA virová * MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza MeSH
- virové proteiny MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- amplifikace genu MeSH
- epidemiologické metody MeSH
- genotyp MeSH
- Hantavirus MeSH
- sérotypizace MeSH
- Geografické názvy
- Evropa MeSH