Figure 4.

Alterations in eNOS phosphorylation state are involved in CEC dysfunction. (A). Under normal conditions, the PI3K/Akt pathway can promote the phosphorylation of eNOS at the Ser1177 locus and the dephosphorylation of the Thr495 locus, thereby enhancing the binding of eNOS to CaM. Thus, eNOS can be rapidly activated to produce adequate amounts of NO to protect vascular function. (B). However, during severe cerebral ischemia, the PI3K/Akt pathway is inhibited, leading to the altered phosphorylation of eNOS—i.e., dephosphorylation at the Ser1177 locus but phosphorylation at the Thr495 locus, which prevents eNOS from being activated and producing NO, thereby exacerbating the dysfunction of CECs.