Although the modulation of host physiology has been interpreted as an essential process supporting baculovirus propagation, the requirement of energy supply for host antivirus reactions could not be ruled out. Our present study showed that metabolic induction upon AcMNPV (budded virus) infection of Bombyx mori stimulated virus clearance and production of the antivirus protein, gloverin. In addition, we demonstrated that adenosine receptor signaling (AdoR) played an important role in regulating such metabolic reprogramming upon baculovirus infection. By using a second lepidopteran model, Spodoptera frugiperda Sf-21 cells, we demonstrated that the glycolytic induction regulated by adenosine signaling was a conservative mechanism modulating the permissiveness of baculovirus infection. Another interesting finding in our present study is that both BmNPV and AcMNPV infection cause metabolic activation, but it appears that BmNPV infection moderates the level of ATP production, which is in contrast to a dramatic increase upon AcMNPV infection. We identified potential AdoR miRNAs induced by BmNPV infection and concluded that BmNPV may attempt to minimize metabolic activation by suppressing adenosine signaling and further decreasing the host's anti-baculovirus response. Our present study shows that activation of energy synthesis by adenosine signaling upon baculovirus infection is a host physiological response that is essential for supporting the innate immune response against infection.
- MeSH
- adenosin metabolismus MeSH
- adenosintrifosfát biosyntéza MeSH
- bourec metabolismus virologie MeSH
- deoxyglukosa farmakologie MeSH
- energetický metabolismus MeSH
- glykolýza účinky léků genetika MeSH
- hmyzí proteiny metabolismus MeSH
- infekce DNA virem metabolismus virologie MeSH
- interakce hostitele a patogenu imunologie MeSH
- mezibuněčné signální peptidy a proteiny metabolismus MeSH
- nukleopolyhedroviry fyziologie MeSH
- purinergní receptory P1 genetika metabolismus MeSH
- replikace viru účinky léků MeSH
- Sf9 buňky MeSH
- Spodoptera MeSH
- transfekce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Drosophila imaginal disc growth factor 2 (IDGF2) is a member of chitinase-like protein family (CLPs) able to induce the proliferation of imaginal disc cells in vitro. In this study we characterized physiological concentrations and expression of IDGF2 in vivo as well as its impact on the viability and transcriptional profile of Drosophila cells in vitro. We show that IDGF2 is independent of insulin and protects cells from death caused by serum deprivation, toxicity of xenobiotics or high concentrations of extracellular adenosine (Ado) and deoxyadenosine (dAdo). Transcriptional profiling suggested that such cytoprotection is connected with the induction of genes involved in energy metabolism, detoxification and innate immunity. We also show that IDGF2 is an abundant haemolymph component, which is further induced by injury in larval stages. The highest IDGF2 accumulation was found at garland and pericardial nephrocytes supporting its role in organismal defence and detoxification. Our findings provide evidence that IDGF2 is an important trophic factor promoting cellular and organismal survival.
- MeSH
- Drosophila imunologie metabolismus MeSH
- energetický metabolismus * MeSH
- glykoproteiny metabolismus MeSH
- hemolymfa chemie MeSH
- kultivované buňky MeSH
- metabolická inaktivace * MeSH
- přirozená imunita * MeSH
- proteiny Drosophily metabolismus MeSH
- stanovení celkové genové exprese MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Adenosine receptors (AR) belonging to the G protein-coupled receptor family influence a wide range of physiological processes. Recent elucidation of the structure of human A2AR revealed the conserved amino acids necessary for contact with the Ado moiety. However, the selectivity of Ado analogs for AR subtypes is still not well understood. We have shown previously that the Drosophila adenosine receptor (DmAdoR) evokes an increase in cAMP and calcium concentration in heterologous cells. In this study, we have characterized the second-messenger stimulation by endogenous DmAdoR in a Drosophila neuroblast cell line and examined a number of Ado analogs for their ability to interact with DmAdoR. We show that Ado can stimulate cAMP but not calcium levels in Drosophila cells. We found one full and four partial DmAdoR agonists, as well as four antagonists. The employment of the full agonist, 2-chloroadenosine, in flies mimicked in vivo the phenotype of DmAdoR over-expression, whereas the antagonist, SCH58261, rescued the flies from the lethality caused by DmAdoR over-expression. Differences in pharmacological effect of the tested analogs between DmAdoR and human A2AR can be partially explained by the dissimilarity of specific key amino acid residues disclosed by the alignment of these receptors.
- MeSH
- 2-chloradenosin farmakologie MeSH
- adenosin analogy a deriváty farmakologie MeSH
- aminokyseliny metabolismus MeSH
- AMP cyklický fyziologie MeSH
- buněčné linie MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- Drosophila metabolismus MeSH
- křečci praví MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- přežití MeSH
- purinergní receptory P1 fyziologie MeSH
- pyrimidiny farmakologie MeSH
- sekvence aminokyselin MeSH
- signální transdukce fyziologie MeSH
- triazoly farmakologie MeSH
- vápník metabolismus MeSH
- vápníková signalizace účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Adenosine (Ado) is a crucial metabolite that affects a wide range of physiological processes. Key proteins regulating Ado signaling, transport and metabolism are conserved among vertebrates and invertebrates. It is well known that Ado influences proliferation of several vertebrate and invertebrate cells. Here we show that Ado negatively influences viability, changes morphology and mitochondrial polarity of the Drosophila imaginal disc cell line (Cl.8+) via a mechanism exclusively dependent on cellular Ado uptake. High transport of Ado is followed by phosphorylation and ATP production as a part of Ado salvation, which at higher concentrations may interfere with cellular homeostasis. In contrast, hematopoietic cell line Mbn2, which grows well in high Ado concentration, preferentially uses adenosine deaminase as a part of the purine catabolic pathway. Our results show that different types of Drosophila cell lines use different pathways for Ado conversion and suggest that such differences may be an important part of complex mechanisms maintaining energy homeostasis in the body.
- MeSH
- adenosin metabolismus toxicita MeSH
- adenosinkinasa antagonisté a inhibitory metabolismus MeSH
- adenosintrifosfát metabolismus MeSH
- buněčné linie MeSH
- Drosophila cytologie metabolismus MeSH
- energetický metabolismus MeSH
- proliferace buněk MeSH
- uridin metabolismus MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH