The preconditioning modified neuronal expression of apoptosis-related proteins of Bcl-2 superfamily following severe hypobaric hypoxia in rats

The patterns of expression of the Bcl-2, Bax, and Bcl-xL proteins were examined immunocytochemically in rat hippocampus and neocortex after severe hypobaric hypoxia (180 Torr for 3 h) and severe hypoxia preconditioned by intermittent mild hypoxia (360 Torr for 2 h daily, for 3 consecutive days, 24 h prior to severe hypoxia). As revealed by TUNEL assay, severe hypobaric hypoxia produced extensive apoptotic damage to the neurons of hippocampal CA1–CA4 and the neocortex but not the dentate gyrus granule cells. Remarkable posthypoxic up-regulation of Bax expression maximal at 24 h was detected in the CA1–CA4 areas of hippocampus and neocortex 3–72 h after severe hypoxia. The preconditioning to severe hypoxia protected neurons from the posthypoxic apoptotic transformations, the up-regulation of Bax expression, and resulted in persistent overexpression of Bcl-2 and Bcl-xL. We conclude that the protective action of hypoxic preconditioning is at least in part mediated by shifting of neuronal Bax/Bcl-2–Bcl-xL ratio to a favor of antiapoptotic proteins Bcl-2 and Bcl-xL.