Sirtuin Activator and Inhibitor Affect Early Dictyostelium Development upon Starvation

Sirtuin is an evolutionally conserved histone deacetylase. The effects of sirtuin activator, resveratrol and inhibitor, nicotinamide on early Dictyostelium development upon starvation were examined. The cell streaming was appeared at 7 h and tight aggregates was formed at 24 h in control cells under submerged culture. Resveratrol treatment accelerated the development. Cell streaming at 6 h and weak aggregates at 9 h were already observed. While, nicotinamide treatment delayed the development. The initiation of streaming was delayed at 9 h, and the development was still under a cell streaming even after 24 h. Dictyostelium development starts inducing the essential molecules adenylyl cyclase, aca and cAMP pulsing induces cell-surface cAMP receptor (carA). Resveratrol treatment significantly increased the expression level of aca at 4 and 6 h after starvation. Nicotinamide treatment decreased the aca expression level at 4 h and carA expression level at 6 h. The induction of aca upon starvation starts with the transcriptional activation by MybB, a. putative transcription factor. MybB expression recovered the initiation timing of the cell streaming against the effect of nicotinamide, but the aggregates formation was still impaired at 24 h. Resveratrol had no effects on MybB-null mutant cells. Neither streaming nor aggregates formation was observed even after 24 h with low levels of aca expression after starvation by resveratrol treatment. These findings suggest that sirtuins may participate in more than one point of the early developmental processes of Dictyostelium upon starvation