Cadmium induces BNIP3-dependent autophagy in chicken spleen by modulating miR-33-AMPK axis.

Cadmium (Cd), a widespread environmental pollutant, has toxic effects on organs including spleen. However, the underlying mechanisms of Cd induced spleen toxicity and the roles of micro-RNA (miRNA) in this process remain poorly understood. To investigate this, cadmium chloride (CdCl2, 10 mg/kg) was administered in the diet of chickens for 90 days. Electron microscopy, qPCR and Western blot were performed. Results showed that Cd exposure suppressed miR-33-5q which increased the levels of AMPK. Subsequently, significant decrease in AKT/mTOR signaling and HSP70 were observed. Concurrently, levels of NF-κB, p-JNK/JNK increased significantly. Moreover, the expression of BNIP3 and other autophagy markers (LC3-I, LC3-II, Beclin-1) increased significantly. Additionally, the levels of ions (Ca, Cr, Se, Sr, Sn, Ba) and (Na, Mg, V, Fe, Mo, Cu, Zn, Cd) significantly decreased and increased, respectively. Taken together, we conclude that Cd induced the deregulation of miR-33-AMPK axis led to BNIP3-dependent autophagy in chicken spleen through AKT/mTOR and HSP70-NF-κB/JNK signal pathways. In-addition Cd could affect ion homeostasis in chicken spleen.