Cell biology

Neuroprotection

Biology

Brain ischemia

Reactive oxygen species

Endocrinology

Apoptosis

Ischemia

Protein kinase B

Signal transduction

Biochemistry

Phosphorylation

Superoxide dismutase

Oxidative stress

Internal medicine

Pharmacology

Medicine

Chemistry

PI3K/AKT/mTOR pathway

Journal of Cerebral Blood Flow & Metabolism

Reactive oxygen species, derived from hypoxia and reoxygenation during transient focal cerebral ischemia (tFCI), are associated with the signaling pathway that leads to neuronal survival or death, depending on the severity and duration of the ischemic insult. The Akt survival signaling pathway is regulated by oxidative stress and is implicated in activation of nuclear factor-κB(NF-κB). Mild cerebral ischemia in mice was used to induce increased levels of Akt phosphorylation in the cortex and striatum. To clarify the role of Akt activation by NF-κB after tFCI, we injected the specific Akt inhibitor IV that inhibits Akt phosphorylation/activation. Inhibition of Akt phosphorylation induced decreases in sequential NF-κB signaling after 30 mins of tFCI at 1 h. Furthermore, the downstream survival signals of the Akt pathway were also decreased. Akt inhibitor IV increased ischemic infarct volume and apoptotic-related DNA fragmentation. Superoxide production in the ischemic brains of mice pretreated with the Akt inhibitor was higher than in vehicle-treated mice. In addition, those pretreated mice showed a reduction of approximately 33% in copper/zinc-superoxide dismutase expression. We propose that Akt signaling exerts its neuroprotective role by NF-κB activation in oxidative cerebral ischemia in mice.

The Role of Akt Signaling in Oxidative Stress Mediates NF-κB Activation in Mild Transient Focal Cerebral Ischemia