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

Kun Lin Jin, Steven H. Graham, Xiao Ou Mao, Xiangjun He, Tetsuya Nagayama, Roger P. Simon, David A. Greenberg

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1508-1519
Number of pages12
JournalJournal of Neurochemistry
Volume77
Issue number6
DOIs
StatePublished - 5 Jul 2001

Fingerprint

bcl-2-Associated X Protein
Cell death
Rats
Exons
Brain
Cell Death
Messenger RNA
Apoptosis Regulatory Proteins
Alternative Splicing
Gene Library
Hippocampus
Ischemia
Neurons
Wounds and Injuries
Proteins

Keywords

  • Bax
  • Cerebral ischemia
  • Gene expression
  • Neuron
  • Programmed cell death

Cite this

Jin, Kun Lin ; Graham, Steven H. ; Mao, Xiao Ou ; He, Xiangjun ; Nagayama, Tetsuya ; Simon, Roger P. ; Greenberg, David A. / Bax κ, a novel Bax splice variant from ischemic rat brain lacking an ART domain, promotes neuronal cell death. In: Journal of Neurochemistry. 2001 ; Vol. 77, No. 6. pp. 1508-1519.
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Bax κ, a novel Bax splice variant from ischemic rat brain lacking an ART domain, promotes neuronal cell death. / Jin, Kun Lin; Graham, Steven H.; Mao, Xiao Ou; He, Xiangjun; Nagayama, Tetsuya; Simon, Roger P.; Greenberg, David A.

In: Journal of Neurochemistry, Vol. 77, No. 6, 05.07.2001, p. 1508-1519.

Research output: Contribution to journalArticle

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AU - Graham, Steven H.

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AU - Simon, Roger P.

AU - Greenberg, David A.

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