Acetylation of FOXO1 is involved in cadmium-induced rat kidney injury via mediating autophagosome-lysosome fusion blockade and autophagy inhibition

Cadmium (Cd), a potentially toxic elements, has the potential to cause harm to the kidneys. Studies has demonstrated that autophagosome-lysosome fusion blockade and consequent autophagy inhibition is related to Cd-induced kidney injury. Studies indicate that acetylation of forkhead box protein O1 (FOXO1) as a transcriptional factor of lysosomal and autophagy genes, but its roles in Cd-exposed kidney tissues remains unclear till now. Therefore, the present study was conducted to elucidate this issue. Data found that Cd enhances the acetylation level of FOXO1 and inhibits the expression level of silent information regulator 1 (Sirt1, deacetylase of FOXO1). Pharmacological activation of Sirt1 (SRT2104 treatment) decreases Cd-increased acetylation level of FOXO1, enhances Cd-inhibited transcription level of Ras-related protein 7 (Rab7), restores Cd-blocked fusion of autophagosome and lysosome, and alleviates Cd-induced autophagy inhibition. Moreover, data corroborated that inhibiting the acetylation level of FOXO1 is conductive to mitigating Cd-induced kidney injury. Collectively, these results demonstrate that acetylation of FOXO1 mediates the autophagosome-lysosome fusion blockade and autophagy inhibition during Cd-induced kidney injury, while regulating the acetylation level of FOXO1 may be a potential mechanism of treating nephrotoxicity after Cd exposure.