The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein

DP5, which contains a BH3 domain, was cloned as a neuronal apoptosis-induci ng gene. To confirm that DP5 interacts with members of the Bcl-2 family, 29 3T cells were transiently co-transfected with DP5 and Bcl-xl cDNA construct s, and immunoprecipitation was carried out. The 30-kDa Bcl-xl was co-immuno precipitated with Myc-tagged DP5, suggesting that DP5 physically interacts with Bcl-xl in mammalian cells. Previously, we reported that DP5 is induced during neuronal apoptosis in cultured sympathetic neurons. Here, we analyz ed DP5 gene expression and the specific interaction of DP5 with Bcl-xl duri ng neuronal death induced by amyloid-beta protein (A beta), DP5 mRNA was in duced 6 h after treatment with A beta in cultured rat cortical neurons, The protein encoded by DP5 mRNA showed a specific interaction with Bcl-xl, Ind uction of DP5 gene expression was blocked by nifedipine, an inhibitor of L- type voltage-dependent calcium channels, and dantrolene, an inhibitor of ca lcium release from the endoplasmic reticulum, These results suggested that the induction of DP5 mRNA occurs downstream of the increase in cytosolic ca lcium concentration caused by A beta, Moreover, DP5 specifically interacts with Bcl-xl during neuronal apoptosis following exposure to A beta, and its binding could impair the survival-promoting activities of Bcl-xl, Thus, th e induction of DP5 mRNA and the interaction of DP5 and Bcl-xl could play si gnificant roles in neuronal degeneration following exposure to A beta.