Nuclear localization of the hypoxia-regulated pro-apoptotic protein BNIP3 after global brain ischemia in the rat hippocampus

Rainald Schmidt-Kastner, Cristina Aguirre-Chen, Thomas Kietzmann, Isabel Saul, Raul Busto, Myron D. Ginsberg

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The 19 kD interacting protein 3, Nip3/BNIP3, is a pro-apoptotic member of the Bcl-2 family induced during hypoxia via the hypoxia-inducible factor (HIF) 1. BNIP3 has been linked to both apoptotic and necrotic cell death involving mitochondrial permeability transition. Since apoptotic and necrotic mechanisms may occur in brain ischemia, immunohistochemical changes of BNIP3 were studied at 1, 2, 3 and 7 days after transient global brain ischemia (12.5 min) in ventilated normothermic rats. In control brains, BNIP3-like immunoreactivity was moderately strong in neuronal processes or cytoplasm and absent in the nucleus. In the ischemia-vulnerable CA1 neurons, BNIP3-positive granules were seen in the nucleus at 1 and 2 days, and these neurons were damaged at 3 and 7 days. The resistant CA3 neurons showed nuclear BNIP3 labeling by 1 day and then returned to the normal state. BNIP3-positive granules did not overlap with the nucleolus. Constitutively expressed BNIP3 may participate in apoptotic and necrotic processes after brain ischemia. Nuclear location of BNIP3 after brain ischemia indicates a novel role for the regulation of cell survival in neurons or a general disturbance of the nuclear envelope.

Original languageEnglish (US)
Pages (from-to)133-142
Number of pages10
JournalBrain Research
Volume1001
Issue number1-2
DOIs
StatePublished - Mar 19 2004

Keywords

  • Apoptosis
  • Bcl-2 family
  • Hippocampus
  • Nuclear membrane

ASJC Scopus subject areas

  • Neuroscience(all)

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