Benzo(a)pyrene regulates chaperone-mediated autophagy via heat shock protein 90

The Benzo(a)pyrene (Bap) exposure induced oxidative damage, DNA damage and autophagy. To explore the molecular mechanism of BaP-induced autophagy. In these studies, we first found that heat shock protein 90 ( HSP90 ), heat shock cognate 70 ( HSC70 ) and lysosomal-associated membrane protein type 2 receptor ( Lamp-2a ) expressions of C57BL mice lung tissue and A549 cells exposed to BaP were significant increase, as well as Bap induced DNA double-strand breaks (DSBs) and activated DNA damage responses, as evidenced by comet assay and γ-H2AX foci analysis in A549 cells. Our results demonstrated BaP induced CMA and caused DNA damage. Next, we knocked down HSP90 expression by the HSP90 Inhibitor, NVP-AUY 922, exposed or HSP90α shRNA lentivirus transduction in A549 cells. HSC70 and Lamp-2a expressions of these cells exposed to BaP were not significant increase, which showed that BaP inducted CMA was mediated by HSP90. Further, HSP90α shRNA prevented BaP induced of Bap which suggested BaP regulated CMA and caused DNA damage by HSP90. Our results elucidated a new mechanism of BaP regulated CMA through HSP90. * BaP : benzo(a)pyrene; CMA : chaperone-mediated autophagy; HSC70 : heat shock cognate 70; HSP90 : heat shock protein 90; Lamp-2a : lysosomal-associated membrane protein type 2 receptor; MTT : tetramethylazozolium salt; q-PCR : quantitative PCR; shRNA : short hairpin RNA