Neuronal prostaglandin endoperoxide synthase 2 responses to oxygen and glucose deprivation are mediated by mitogen-activated protein kinase ERK1/2.

Abstract:

:Prostanoids in the central nervous system define an important linkage between blood pressure and hormonal responses to hypotension/ischemia. Prostaglandin endoperoxide synthase (PGHS)-2, the inducible isoform of this enzyme, is induced by cerebral hypoperfusion/ischemia. To investigate the mechanism of the PGHS-2 gene expression in response to cerebral hypoperfusion/ischemia in neurons, we used a cell culture model (human SK-N-AS cells) to mimic the oxygen and glucose deprivation (OGD) that usually results from ischemia. Whereas OGD stimulated robust increases in PGHS-2 mRNA abundance, neither oxygen nor glucose deprivation alone was effective. Our data demonstrated that induction of both PGHS-2 mRNA and protein reached peak levels ( approximately 10 fold) after 6 h OGD. This was partially blocked by the inhibition of mitogen-activated protein kinase (MAPK) p38, and was almost completely blocked by the inhibition of extracellular signal-related kinases 1/2 (ERK1/2 or p44/42), another MAPK. These results indicate that PGHS-2 gene expression is induced by oxygen and glucose deprivation synergistically in neurons, and this induction is mediated by one or more members of the MAPK family.

journal_name

Brain Res

journal_title

Brain research

authors

Zhang D,Wood CE

doi

10.1016/j.brainres.2005.08.033

subject

Has Abstract

pub_date

2005-10-26 00:00:00

pages

100-7

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(05)01214-X

journal_volume

1060

pub_type

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