Brain genomic response following hypoxia and re-oxygenation in the neonatal rat: Identification of genes that might contribute to hypoxia-induced ischemic tolerance

Myriam Bernaudin, Yang Tang, Melinda Reilly, Edwige Petit, Frank R Sharp

Research output: Contribution to journalArticle

256 Citations (Scopus)

Abstract

Hypoxic preconditioning (8% 02, 3 h) produces tolerance 24 h after hypoxic-ischemic brain injury in neonatal rats. To better understand the ischemic tolerance mechanisms induced by hypoxia, we used oligonucleotide microarrays to examine genomic responses in neonatal rat brain following 3 h of hypoxia (8% 02) and either 0, 6, 18, or 24 h of re-oxygenation. The results showed that hypoxia-inducible factor (HIF)-1-but not HIF-2-mediated gene expression may be involved in brain hypoxia-induced tolerance. Among the genes regulated by hypoxia, 12 genes were confirmed by real time reverse transcriptase-PCR as follows: VEGF, EPO, GLUT-1, adrenomedullin, propyl 4-hydroxylase α, MT-1, MKP-1, CELF, 12-lipoxygenase, t-PA, CAR-1, and an expressed sequence tag. Some genes, for example GLUT-1, MT-1, CELF, MKP-1, and t-PA did not show any hypoxic regulation in either astrocytes or neurons, suggesting that other cells are responsible for the up-regulation of these genes in the hypoxic brain. These genes were expressed in normal and hypoxic brain, heart, kidney, liver, and lung, with adrenomedullin, MT-1, and VEGF being prominently induced in brain by hypoxia. These results suggest that a number of endogenous molecular mechanisms may explain how hypoxic preconditioning protects against subsequent ischemia, and may provide novel therapeutic targets for treatment of cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)39728-39738
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number42
DOIs
StatePublished - Oct 18 2002
Externally publishedYes

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Oxygenation
Rats
Brain
Genes
Adrenomedullin
Brain Hypoxia
Vascular Endothelial Growth Factor A
Arachidonate 12-Lipoxygenase
Hypoxia-Inducible Factor 1
Expressed Sequence Tags
Mixed Function Oxygenases
Oligonucleotide Array Sequence Analysis
Brain Ischemia
Reverse Transcriptase Polymerase Chain Reaction
Astrocytes
RNA-Directed DNA Polymerase
Brain Injuries
Microarrays
Real-Time Polymerase Chain Reaction
Gene expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Brain genomic response following hypoxia and re-oxygenation in the neonatal rat : Identification of genes that might contribute to hypoxia-induced ischemic tolerance. / Bernaudin, Myriam; Tang, Yang; Reilly, Melinda; Petit, Edwige; Sharp, Frank R.

In: Journal of Biological Chemistry, Vol. 277, No. 42, 18.10.2002, p. 39728-39738.

Research output: Contribution to journalArticle

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