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Cyclooxygenase 2 inhibits SAPK activation in neuronal apoptosis. Biochem Biophys Res Commun 2003 Jan 24;300(4):884-8

Date

02/01/2003

Pubmed ID

12559955

DOI

10.1016/s0006-291x(02)02947-9

Scopus ID

2-s2.0-0037462978 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

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 A

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
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