Sodium selenite-induced activation of DAPK promotes autophagy in human leukemia HL60 cells

Abstract

Autophagy has been suggested as a possible mechanism fornon-apoptotic death despite evidence from many species thatautophagy represents a survival strategy of cells under stress.From our previous findings that supranutritional doses ofsodium selenite induced apoptosis in human leukemia cells,now we show autophagic cell death occurred after seleniteexposure in HL60, suggested an alternative mechanism for thepotential therapeutic properties of selenite. Additionally,Death-associated Protein Kinase (DAPK) performed a significantlyincreased expression during this process, concomitantlywith gradually decreased phosphorylation at Ser308. We furtherreveal that the up-regulation of DAPK which depends onselenite-activated ERK had no effect on autophagy. However,activation of DAPK via PP2A-mediated dephosphorylation atSer308 serves as a new strategy for autophagy induction. Inconclusion, these results indicate that PP2A-mediated activatedDAPK sensitizes HL60 cells to selenite, ultimately triggersautophagic cell death pathway to commit cell demise. [BMBreports 2012; 45(3): 194-199]

Keywords

• Autophagy
• DAPK
• HL60
• PP2A
• Sodium selenite