Nickel induces autophagy via PI3K/AKT/mTOR and AMPK pathways in mouse kidney

Nickel (Ni), a widely distributed metal, is an important pollutant in the environment. Although kidney is a crucial target of Ni toxicity, information on autophagy and the potential mechanisms of Ni-induced renal toxicity are still poorly described. As we discovered, NiCl₂ could induce renal damage including decrease in renal weight, renal histological alterations, and renal function injury. According to the obtained results, NiCl₂ could obviously increase autophagy, which was characterized by increase of LC3 expression and decrease of p62 expression. Meanwhile, the result of ultrastructure observation showed increased autolysosomes numbers in the kidney of NiCl₂-treated mice. In addition, NiCl₂ increased mRNA and protein levels of autophagy flux proteins including Beclin1, Atg5, Atg12, Atg16L1, Atg7, and Atg3. Furthermore, NiCl₂ induced autophagy through AMPK and PI3K/AKT/mTOR pathways which featured down-regulated expression levels of p-PI3K, p-AKT and p-mTOR and up-regulated expression levels of p-AMPK and p-ULK1. In summary, the above results indicate involvement of autophagy in renal injury induced by NiCl₂, and NiCl₂ induced autophagy via PI3K/AKT/mTOR and AMPK pathways in mouse kidney.