Prostaglandin D2 synthase induces apoptosis in PC12 neuronal cells.
Apoptosis of neuronal cells is a proposed cause of certain neurological disorders. Here, we report on a 5- to 6-fold increase in apoptosis by exposure to prostaglandin D2 synthase (PGD2S) in PC12 neuronal cells. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, and appears to be mediated via caspase-3 activation. Neutralization with anti-PGD2S antibody or pre-treatment with selenium, which inhibits PGD2S enzymatic activity, both significantly inhibited the PGD2S-induced apoptosis, however, neither had any effect on the apoptosis induced by the known neuronal apoptotic inducer, glutamate. In addition, prostaglandins E1, E2, and F2alpha all inhibited the PGD2S-induced apoptosis while prostaglandin H2 had no significant effect. Furthermore, PGD2S isolated from human serum was more effective at inducing apoptosis then recombinantly expressed protein, presumably due to glycosylation. This novel role of PGD2S, as an inducer of apoptosis, may have implications in PC12 differentiation and possibly some neurological disorders.
Ragolia
L
L
1Department of Medicine, Division of Cell Biology, Winthrop-University Hospital, 222 Station Plaza North, Suite 505-B, Mineola, NY 11501, USA.
Palaia
T
T
Frese
L
L
Fishbane
S
S
Maesaka
J K
JK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D020287:In Situ Nick-End Labeling; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D054834:Lipocalins; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000906:Antibodies; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D054834:Lipocalins; D011453:Prostaglandins; D011994:Recombinant Proteins; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase