Differential Expression of BNIP Family Members of BH3-only Proteins During the Development and After Axotomy in the Rat

The BNIPs (BCL2 and adenovirus E1B 19 kDa interacting proteins) are a subfamily of BCL2 family proteins typically containing a single BCL2 homology 3 (BH3) domain. BNIPs exert important roles in two major degradation processes in cells - apoptosis and autophagy. Although it is known that the function of BNIPs is transcriptionally regulated under hypoxic conditions in tumors, their regulation in the developing brain and neurons following the induction of apoptosis/autophagy is largely unknown. In this study, we demonstrate that three members of the BNIP family, BNIP1, BNIP3 and BNIP3L, are expressed in the developing brain with distinct brain region specificity. BNIP3 mRNA was especially enriched in the entorhinal cortex, raising a possibility that it may have additional biological functions in addition to its apoptotic and autophagic functions. Following starvation-induced autophagy induction, BNIP1 mRNA was selectively increased in cultured neurons. However, the apoptogenic chemical staurosporine failed to modulate the expression of BNIPs, which is in contrast to the marked induction of all BNIPs by glucose-oxygen deprivation. Finally, neonatal nerve axotomy, which triggers apoptosis in motoneurons, selectively enhanced BNIP3 mRNA expression. Collectively, these results suggest that the expression of BNIPs is differentially regulated depending on the stimuli, and BNIPs may exert unique biological functions.