Bax κ, a novel Bax splice variant from ischemic rat brain lacking an ART domain, promotes neuronal cell death

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Abstract
Bax is a pro‐apoptotic Bcl‐2 family protein that regulates programmed cell death through homodimerization and through heterodimerization with Bcl‐2. Bax α is encoded by six exons and undergoes alternative splicing. Bax κ, a splice variant of Bax with conserved BH1, BH2 and BH3 binding domains and a C‐terminal transmembrane domain (TM), but with an extra 446‐bp insert between exons 1 and 2 leading to loss of an N‐terminal ART domain, was identified from an ischemic rat brain cDNA library. Expression of Bax κ mRNA and protein was up‐regulated in hippocampus after cerebral ischemic injury. The increased Bax κ mRNA was distributed mainly in selectively vulnerable hippocampal CA1 neurons that are destined to die after global ischemia. Overexpression of Bax κ protein in HN33 mouse hippocampal neuronal cells induced cell death, which was partially abrogated by co‐overexpression of Bcl‐2. Moreover, co‐overexpression of Bax κ and Bax α increased HN33 cell death. The results suggest that the Bax κ may have a role in ischemic neuronal death.