Cyclooxygenase 2 inhibits SAPK activation in neuronal apoptosis. Biochem Biophys Res Commun 2003 Jan 24;300(4):884-8
Date
02/01/2003Pubmed ID
12559955DOI
10.1016/s0006-291x(02)02947-9Scopus ID
2-s2.0-0037462978 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Cyclooxygenase 2 (COX-2) expressed in cultured neuronal PC12 cells under inducible promoter protects cells from trophic withdrawal apoptosis. Stimulation of SAPK is thought to play a significant role in initiation of PC12 cell death. We have therefore examined whether COX-2 expression inhibits trophic withdrawal-mediated activation of SAPK. SAPK activity increased during the first 6h after NGF removal in mock-transfected PC12 cells. COX-2 expression attenuated the increase of SAPK, as detected by Western blot analysis with phosphorylation state specific anti-SAPK antibodies and by SAPK activity assays. We propose that COX-2 attenuated SAPK activation by preventing activation of nNOS, which occurs, as we have shown before, via COX-2-mediated expression of dynein light chain (DLC). Activation of SAPK in neuronal cell death was attenuated by DLC expression. These observations support a role for NO production and SAPK activation in the neuronal death mechanisms.
Author List
Miller B, Chang YW, Sorokin AAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Carrier Proteins
Caspase 3
Caspases
Culture Media
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Drosophila Proteins
Dyneins
Enzyme Activation
Enzyme Inhibitors
Indomethacin
Isoenzymes
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 8
Mitogen-Activated Protein Kinases
Nerve Growth Factor
Neurons
Nitric Oxide Donors
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
PC12 Cells
Prostaglandin-Endoperoxide Synthases
Rats
p38 Mitogen-Activated Protein Kinases