Proteins of Bcl-2 family are crucial regulators of intrinsic (mitochondrial) pathway of apoptosis that is implicated among the mechanisms of ischemic neuronal death. Initiation of mitochondrial apoptosis depends on changes of equilibrium between anti-apoptotic and
pro-apoptotic proteins of Bcl-2 family as well as on translocation of
pro-apoptotic proteins of Bcl-2 family to mitochondria. The aim of this work was to study the effect of transient global
brain ischemia on expression and intracellular distribution of
proteins of Bcl-2 family in relation to the
ischemia-induced changes of ERK and Akt
kinase pathways as well as disturbances in
ubiquitin proteasome system. Using four vessel occlusion model of transient global
brain ischemia, we have shown that both
ischemia in duration of 15 min and the same
ischemia followed by 1, 3, 24, and 72 h of reperfusion did not affect the levels of either pro-apoptotic (Bad, PUMA, Bim, Bax, Noxa) or anti-apoptotic (Bcl-2, Bcl-xl, Mcl-1)
proteins of Bcl-2 family in total
cell extracts from rat hippocampus. However, significantly elevated level of
Bad protein in the mitochondria isolated from rat hippocampus was observed already 1 h after
ischemia and remained elevated 3 and 24 h after
ischemia. We did not observe significant changes of the levels of Puma, Bax, Bcl-2, and Bcl-xl in the mitochondria after
ischemia and
ischemia followed by reperfusion. Our results might indicate possible involvement of Bad translocation to mitochondria in the mechanisms of neuronal death following transient global
brain ischemia.