CIIA negatively regulates neuronal cell death induced by oxygen-glucose deprivation and reoxygenation.

Brain ischemia causes neuronal injury leading to stroke and other related brain diseases. However, the precise mechanism of the ischemia-induced neuronal death remains unclear yet. In this study, we showed that CIIA suppressed neuronal cell death induced by oxygen and glucose deprivation followed by reoxygenation (OGD/R), which mimics ischemia and reperfusion in vivo, in neuroblastoma cell lines as well as primary cortical neurons. Furthermore, CIIA inhibited the OGD/R-induced stimulation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream kinases including c-Jun amino-terminal kinase and p38 kinase, concomitantly blocking ASK1 homo-oligomerization and the binding between ASK1 and TRAF2. CIIA also repressed the OGD/R-induced activation of caspase-3 in neuronal cells. Taken together, our results suggest that CIIA attenuates neurotoxicity caused by OGD/R through inhibiting ASK1-dependent signaling events.