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Bax κ, a novel Bax splice variant from ischemic rat brain lacking an ART domain, promotes neuronal cell death
Author(s) -
Jin Kun Lin,
Graham Steven H.,
Mao Xiao Ou,
He Xiangjun,
Nagayama Tetsuya,
Simon Roger P.,
Greenberg David A.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00361.x
Subject(s) - alternative splicing , programmed cell death , exon , hippocampal formation , bcl 2 associated x protein , microbiology and biotechnology , biology , apoptosis , rna splicing , messenger rna , gene , neuroscience , genetics , rna , caspase 3
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.