RESUMEN
Survival and adaptation to oxidative stress is important for many organisms, and these occur through the activation of many different signaling pathways. In this report, we showed that Caenorhabditis (C.) elegans G protein-coupled receptor kinases modified the ability of the organism to resist oxidative stress. In acute oxidative stress studies using juglone, loss-of-function grk-2 mutants were more resistant to oxidative stress compared with loss-of-function grk-1 mutants and the wild-type N2 animals. This effect was Ce-AKT-1 dependent, suggesting that Ce-GRK2 adjusted C. elegans oxidative stress resistance through the IGF/insulin-like signaling (IIS) pathway. Treating C. elegans with a GRK2 inhibitor, the selective serotonin reuptake inhibitor paroxetine, resulted in increased acute oxidative stress resistance compared with another selective serotonin reuptake inhibitor, fluoxetine. In chronic oxidative stress studies with paraquat, both grk-1 and grk-2 mutants had longer lifespan compared with the wild-type N2 animals in stress. In summary, this research showed the importance of both GRKs, especially GRK2, in modifying oxidative stress resistance.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Estrés Oxidativo , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Quinasa 2 del Receptor Acoplado a Proteína-G/genética , Longevidad , Mutación con Pérdida de FunciónRESUMEN
In this report, we explored if G protein coupled receptor kinases (GRKs) can help modulate the heat stress responses of Caenorhabditis (C.) elegans. Loss of function grk-2 C. elegans mutants were more tolerant to increases in heat and display an ability for heat stress-associated hormesis at a longer exposure time unlike the wild type N2 animals and the loss of function grk-1 C. elegans mutants. The loss of function grk-1 mutants recovered more from acute heat stress compared to the wild type N2 animals. Animals with low Ce-GRK2 protein expression showed increased DAF-16 nuclear localization during the early stages of heat stress exposure compared to the other RNAi-treated animals, demonstrating altered insulin/insulin-like growth factor signaling (IIS) pathway activity in response to the stress. pdk-1 and akt-1 may play key roles in conjunction with Ce-GRK2 in the heat stress response. Collectively, these findings demonstrate that GRKs influence C. elegans heat stress behaviors.
