Expression of poly(C)-binding proteins is differentially regulated by hypoxia and ischemia in cortical neurons

Y. Zhu, Y. Sun, X. O. Mao, K. L. Jin, D. A. Greenberg

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Hypoxia and ischemia regulate the expression of several important genes at the level of transcription and of mRNA stability. Two isoforms of a 40-kDa poly(C)-binding protein, previously identified as RNA-binding proteins, bind to a hypoxia-inducible protein-binding site in the 3′-untranslated region of erythropoietin and tyrosine hydroxylase mRNAs and regulate mRNA stability. To determine if poly(C)-binding proteins show changes in expression - which might regulate mRNA stability - in hypoxic or ischemic neuronal cells, we examined poly(C)-binding protein 1 and poly(C)-binding protein 2 expression in hypoxic cortical neuron cultures and in rat cerebral cortex after focal ischemia. Reverse transcription-polymerase chain reaction and western blotting showed hypoxic up-regulation of poly(C)-binding protein 1, and down-regulation of poly(C)-binding protein 2, mRNA and protein expression. Hypoxia-inducible expression of poly(C)-binding protein 1 was mediated by p38 mitogen-activated protein kinase, while hypoxia-reducible expression of poly(C)-binding protein 2 was mediated by protein kinase C. Immunostaining showed that poly(C)-binding protein 1, but not poly(C)-binding protein 2, expression was increased in the ischemic boundary zone (penumbra) of the frontal cortex after 90 min of ischemia, and persisted for at least 72 h after reperfusion. These results demonstrate that poly(C)-binding protein 1 and poly(C)-binding protein 2 in cortical neurons are differentially affected by hypoxic/ischemic insults, suggesting that there are functional differences between poly(C)-binding protein isoforms. Since we observed no poly(C)-binding protein expression in astroglia, alternative mRNA stability mechanisms may exist in these cells.

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalNeuroscience
Volume110
Issue number2
DOIs
StatePublished - 12 Mar 2002

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