카드뮴 내성에 있어서 자가포식현상

Abstract

To elucidate the mechanisms involved in resistance of lung epithelial cells to cadmium, we established a cell line that exhibits cadmium-resistance (RWI38). RWI38 cells showed 5-fold greater cadmium-resistance than WI38 cells, and upregulated multidrug resistance-associated protein (MRP) and metallothionein in respond to cadmium. Cadmium induced Akt phosphorylation in RWI38 cells but not in WI38 cells; this was prevented by using of pharmacological MRP inhibitor, probenecid, or siRNA for MRP, both of which enhanced cell death and capsase-3 activation. Cadmium-treated RWI38 cells induced autophagy, as demonstrated by Atg5 induction, LC3 conversion, and formation of GFP?LC3 dots. A pharmacological autophagy inhibitor, 3-methyladenine, or silencing of atg5 gene downregulated the cadmium-indu ced Akt phosphorylation and MRP, and further enhanced procaspase-3 clevage. However, pharmacological or genetic inhibition of mrp-1 had no effect on cadmium-induced LC3 II induction. These data indicate that cadmium-induced autophagy is involved in cell protection by blocking of apoptosis through MRP-Akt signaling pathway.