Carbofuran affects cellular autophagy and developmental senescence through the impairment of Nrf2 signalling

Carbofuran is a broad‐spectrum synthetic pesticide. Its exposure to non‐target mammals affects the biological system through the induction of oxidative stress. Since oxidative stress is a major contributing factor to cellular autophagy and senescence, our present investigation determined the impacts of carbofuran‐induced oxidative stress on cellular autophagy and senescence. A transmembrane protein, Spinster homolog 1 (Spns1), is involved in autophagic lysosomal metabolism. Its mutation accelerates the cellular senescence and shortens the lifespan. Using a transgenic zebrafish line, expressing fluorescent microtubules‐associated protein 1 light chain 3 (EGFP‐LC3) at the membrane of the autophagosome, we found that carbofuran affects autophagic lysosomal biogenesis in wild‐type zebrafish and exacerbates autophagic defect in spns1‐mutant zebrafish. In real‐time mortality study, carbofuran has shortened the lifespan of wild‐type fish. Nrf2 is a stress‐responsive transcription factor that regulates the expression of antioxidant genes (such as gstp1) in the prevention of oxidative stress‐mediated cellular damage. To assess the effect of carbofuran on Nrf2 signalling, we established a dual‐monitoring transgenic zebrafish line, expressing gstp1 promoter‐driven EGFP and mCherry‐tagged Neh2 domain of Nrf2. Our results suggested that the exposure of carbofuran has down‐regulated both Nrf2 and Gstp1 expressions. Overall, carbofuran affects cellular autophagy and accelerates senescence by enervating the Nrf2 signalling.