Bcl-2 family members make different contributions to cell death in hypoxia and/or hyperoxia in rat cerebral cortex

Xiaoming Hu, Jingxin Qiu, Marjorie R. Grafe, Harriett C. Rea, David K. Rassin, J. Regino Perez-Polo

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Hypoxic brain injury during fetal or neonatal development leads to damaged immature neurons and can result in cognitive or behavioral dysfunction. Hyperoxia therapy (treatment with oxygen) is commonly applied to infants with signs of perinatal hypoxia-anoxia. Both hypoxia and hyperoxia have been shown to result in apoptosis in the brains of rats in several animal models. One determinant of cellular commitment to cell death is the differential expression of the Bcl-2 family of proteins in response to trauma. Here, we characterize cell death and the expression of Bcl-2 homologous proteins in 7-day-old neonatal rat cerebral cortex after hypoxia (5% O2 for 40min) and/or hyperoxia (>95% O2 for 2h after hypoxia). The expression of Bcl-2 and Bcl-XL, two anti-apoptotic proteins, decreased at 24 h after hypoxia. Bcl-XL increased after either hyperoxia or hypoxia+hyperoxia. We did not detect significant changes in the cytoplasmic levels of pro-apoptotic protein Bax after any of these three treatments. Using cell death ELISA and DNA FragEL© assays, we observed increased cell death at 24h after hypoxia, hyperoxia or hypoxia+hyperoxia treatments. At 24h after either hypoxia, hyperoxia or hypoxia+hyperoxia, caspase 3 activity also increased significantly. Our results suggest that both hypoxia and hyperoxia alone can induce cell death. The Bcl-2 → cytochrome c → caspase 3 pathway played a role in hypoxia-induced cell death, while other pathways may be involved in hyperoxia-induced cell death.

Original languageEnglish (US)
Pages (from-to)371-377
Number of pages7
JournalInternational Journal of Developmental Neuroscience
Volume21
Issue number7
DOIs
StatePublished - Nov 2003

Keywords

  • Bax
  • Bcl-2
  • Bcl-X
  • Cell death
  • Cortex
  • Hyperoxia
  • Hypoxia

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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