RESUMO
O-GlcNAcylation is a dynamic post-translational modification that takes place on ser/thr residues of nucleocytoplasmic proteins. O-GlcNAcylation regulates almost all cellular events as a nutrient sensor, a transcriptional and translational regulator, and a disease-related factor. Although the role of O-GlcNAcylation in insulin signaling and metabolism are well established, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we manipulated O-GlcNAcylation in Drosophila and found that it regulates autophagy through Akt/dFOXO signaling. We demonstrate that O-GlcNAcylation and the levels of O-GlcNAc transferase (OGT) are increased during starvation. Furthermore, Atg proteins and autolysosomes are increased in OGT-reduced flies without fasting. Atg proteins and autophagosomes are reduced in OGT-overexpressing flies. Our results suggest that not only autophagy gene expression but also autophagic structures are regulated by OGT through Akt and dFOXO. These data imply that O-GlcNAcylation is important in modulating autophagy as well as insulin signaling in Drosophila.
Assuntos
Autofagia/fisiologia , Drosophila melanogaster/fisiologia , Insulina/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Transdução de Sinais/fisiologia , Inanição/metabolismo , Animais , Linhagem Celular , Primers do DNA/genética , Proteínas de Drosophila/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Immunoblotting , Imuno-Histoquímica , Imunoprecipitação , Microscopia Eletrônica de Transmissão , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piranos , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , TiazóisRESUMO
The involvement of neutrophils in the lungs during the recovery phase of coronavirus disease 2019 (COVID-19) is not well defined mainly due to the limited accessibility of lung tissues from COVID-19 survivors. The lack of an appropriate small animal model has affected the development of effective therapeutic strategies. We here developed a long COVID mouse model to study changes in neutrophil phenotype and association with lung injury. Our data shows persistent neutrophil recruitment and neutrophil extracellular trap formation in the lungs for up to 30 days post-infection which correlates with lung fibrosis and inflammation.