PC12 cells and primary neurons, or PC12 cells infected with lentiviral shRNA to CaMKII or GFP (as control), were treated with rotenone (0.5 and 1 μM) for 24 h, or pretreated with/without KN93 (10 μM) for 1 h and then exposed to rotenone (0.5 and 1 μM) for 24 h. Total cell lysates were subjected to Western blotting using indicated antibodies (A, C, D) The blots were probed for β-tubulin as a loading control. Similar results were observed in at least three independent experiments. Cell apoptosis was assayed using DAPI staining (B, E). A., B. Inhibition of CaMKII by KN93 partially prevented inhibition of mTOR, S6K and 4E-BP1 phosphorylation, cleavage of-caspase-3 (A) and apoptosis (B) in the cells induced by rotenone. C.-E. Lentiviral shRNA to CaMKII, but not to GFP, down-regulated CaMKII expression by ∼90% in PC12 cells (C), which obviously attenuated retonone-induced phosphorylation of CaMKII, and conferred partial resistance to rotenone-induced inhibition of mTOR signaling and activation of caspase-3 (D), as well as apoptosis (E) in the cells. Results are presented as mean ± SE (n = 5). aP < 0.05, difference with control group; bP < 0.05, difference with 0.5 μM rotenone group; cP < 0.05, difference with 1 μM rotenone group; dP < 0.05, CaMKII shRNA group versus GFP shRNA group.