Cyclooxygenase-2 expression inhibits trophic withdrawal apoptosis in nerve growth factor-differentiated PC12 cells. J Biol Chem 2000 Apr 21;275(16):12095-101
Date
04/15/2000Pubmed ID
10766843DOI
10.1074/jbc.275.16.12095Scopus ID
2-s2.0-0034697126 (requires institutional sign-in at Scopus site) 84 CitationsAbstract
Cyclooxygenase-2 (Cox-2), an enzyme responsible for catalyzing the committed step in prostanoid biosynthesis, is the product of an immediate early gene capable of being up-regulated by diverse stimuli. Significantly Cox-2 mRNA is absent from rat pheochromocytoma (PC12) cells, both basally and following stimulation with a range of agonists. Using PC12 cells engineered to stably express isopropyl-1-thio-beta-D-galactopyranoside-inducible Cox-2 (PCXII-4), we have investigated the putative effects of Cox-2 expression on differentiation, proliferation, and trophic withdrawal apoptosis. Cox-2 bioactivity had no effect on nerve growth factor-induced differentiation, epidermal growth factor-induced proliferation, or aromatic L-amino acid decarboxylase expression. However, trophic withdrawal apoptosis, induced by the removal of nerve growth factor following differentiation, was markedly reduced in the PCXII-4 when compared with control cells, as assessed by annexin V staining, DNA laddering, and Hoechst 33258 staining. The specificity of this effect was confirmed using two pharmacologically distinct nonsteroidal anti-inflammatory drugs, indomethacin and NS398. Investigations showed that the activity of the pro-apoptotic protease caspase-3 was reduced in PCXII cells. This study demonstrates that Cox-2-derived prostaglandins exert cytoprotective effects in trophic factor withdrawal apoptosis and provides evidence that this is, at least in part, due to suppression of caspase-3 activity.
Author List
McGinty A, Chang YW, Sorokin A, Bokemeyer D, Dunn MJAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Caspase 3
Caspases
Cell Differentiation
Cyclooxygenase 2
Enzyme Induction
Epidermal Growth Factor
Isoenzymes
Isopropyl Thiogalactoside
Nerve Growth Factors
PC12 Cells
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Rats