A Pathway of Neuronal Apoptosis Induced by Hypoxia/Reoxygenation.

As a model of the reperfusion injury found in stroke, we have exposed neurons to hypoxia followed by reoxygenation. Neurons treated with hypoxia/reoxygenation (H/R) respond by activating nuclear factor-κB (NFκB), releasing cytochrome c from their mitochondria, and ultimately dying. Further supporting an apoptotic mechanism, expression of the antiapoptotic Bcl-2 and Bcl-x proteins was increased following H/R. In this model, adenoviral-mediated transduction of lκB expression inhibited NFκB activation and significantly accelerated cytochrome c release and caspase-dependent neuronal death. At the same time, expression of mutated lκB prevented the increased expression of endogenous Bcl-2 and Bcl-x. In the presence of mutated lκB, singular overexpression of only Bcl-2 by adenoviral-mediated transduction significantly inhibited cytochrome c release, caspase-3-like activation, and cell death in response to H/R. These findings suggest a pathway where NFκB activation induces overexpression of Bcl-2 and Bcl-x, which function to prevent apoptotic cell death following H/R treatments. [ABSTRACT FROM AUTHOR]