Neuronal prostaglandin endoperoxide synthase 2 responses to oxygen and glucose deprivation are mediated by mitogen-activated protein kinase ERK1/2.
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.
Zhang
Daying
D
Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610-0264, USA. dzhang@phys.med.ufl.edu
Wood
Charles E
CE
D015153:Blotting, Western; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose