Figure 3.

HDAC3-induced neurotoxicity is inhibited by IGF-1 and activation of the PI-3 kinase–Akt signaling pathway. A, CGNs were transfected with HDAC3-Flag alone or in combination with a plasmid expressing HA-tagged constitutively active Akt (CA-Akt-HA). The transfected cultures were then treated with no additives or with IGF-1. B, CGNs were transfected with HDAC3-Flag and then treated with no additives or with IGF-1, IGF-1, and wortmannin, or IGF-1 and LY294002. Eight hours later, the cultures were switched to serum-free medium containing inhibitors, and cell viability assessed 24 h later. C, CGNs were transfected with HDAC3-Flag and treated with HK medium containing either no additives, supplemented with JNK inhibitor (SP600125), CDK inhibitor (roscovitine), GSK3 inhibitor (SB415826 or SB216763), or cotransfected with a dominant-negative form of GSK3β (GSK3β-K85A). Cell viability was assessed 24 h after switching to HK medium. Viability in all cases was normalized to control cultures, which were transfected with GFP and treated with HK medium. *p < 0.01.