Duox-driven ROS release by glia promote regeneration in the adult Drosophila brain
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE309567 | GEO | 2026/02/09
REPOSITORIES: GEO
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Project description:Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We have identified and validated a collection of circular RNAs in Drosophila melanogaster. We show that the circular RNA circ_ATP8B is induced by viral infection and that depletion of circ_ATP8B, but not its linear sibling, compromises viral infection both in cultured cells and in vivo. In addition, our analyses reveal that circ_ATP8B is enriched in the fly gut and that gut-specific depletion of circ_ATP8B attenuates viral replication in an oral infection model. Furthermore, we find circ_ATP8B-depletion resulted in increased levels of reactive oxygen species (ROS) and enhanced expression of Duox (Dual oxidase), which produces ROS. Genetic and pharmacological manipulation of circ_ATP8B-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circ_ATP8B depletion. Notably, circ_ATP8B and Duox associate with each other, and that expression of various versions of circ_ATP8B that are competent in binding Duox, but not a mutant circ_ATP8B that is incapable of binding Duox, restores physiological levels of ROS in circ_ATP8B-depleted cells. Lastly, our data show that Gaq, a subunit of G protein required for optimal Duox activity, acts downstream of circ_ATP8B to regulate Duox activity. We conclude that circ_ATP8B regulates anti-viral immunity by modulating Duox-dependent ROS production.
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Project description:Aims: Vascular wall resident stem cells (SCs) hold great promise for cardiovascular regenerative therapy. This study evaluated the impact of oxidative stress on the viability and functionality of saphenous vein'derived pericytes (SVPs), SVPs'deriv ed cells and terminally differentiated vascular cells. We also investigated the molecular mechanisms underlying the SVP resistance to oxidative stress. Results: SVPs exhibit a significantly higher resistance to oxidative stress resulting in reduced apoptosis upon exposure to hydrogen peroxide in comparison to endothelial cells (ECs). This was attributed to upregulation of genes encoding for anti'oxidant enzymes, especially superoxide dismutases (SODs) and catalase. Pharmacological inhibition of SODs increased ROS levels in SVPs and impaired their survival. Furthermore, we confirm that, when exposed to differentiation stimuli, SVPs are able to generate mesodermic lineages. Interestingly, differentiation of SVPs resulted in SOD down'regulation and increased apoptosis upon exposure to hydrogen peroxide. Oxidative stress caused an incremental increase on SVPs migration, whilst being inhibitory for the ECs. Additionally, oxidative stress did not impair SVPs capacity to promote angiogenesis in vitro. Innovations: This study for the first time demonstrates that SCs resident in veins of cardiovascular patients are endowed with enhanced detoxifier and antioxidant system. Conclusions: SVPs expanded from vein remnants of coronary artery bypass graft surgery express antioxidant defense mechanisms which allow them resist to high levels of ROS. These properties highlight the potential of SVPs in cardiovascular regenerative medicine.
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