FIGURE 9.

Schematic representation of the role of SIRT1 in C5b-9-mediated cell cycle activation in OLGs. Our results show that sublytic C5b-9 induces the expression of NG2/CSPG4, a marker for OPCs, and mediates cell cycle activation by inducing SIRT1 through the c-jun, protein kinase C, and PI3K/Akt signaling pathways. In addition, sublytic C5b-9 was found to significantly down-regulate the expression of MBP and PLP. SIRT1 is known to deacetylate lysine 9 of histone H3 and indirectly promotes its trimethylation (H3K9me3), resulting in a facultative heterochromatin state. We speculate that this result leads to the transcriptional inhibition of cell cycle inhibitors, allowing for the expression of cyclin D1 and promoting cell cycle activation. Sublytic C5b-9 also activates proto-oncogenes, leading to transcriptional and cell cycle activation. Inhibition of c-jun with antisense c-jun leads to inhibition of sublytic C5b-9-induced SIRT1 expression and cell cycle activation.