Prostaglandin D-2 synthase induces apoptosis in PC12 neuronal cells

Apoptosis of neuronal cells is a proposed cause of certain neurological dis orders. Here, we report on a 5- to 6-fold increase in apoptosis by exposure to prostaglandin D-2 synthase (PGD(2)S) in PC12 neuronal cells. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP n ick end-labeling (TUNEL) assay, and appears to be mediated via caspase-3 ac tivation. Neutralization with anti-PGD(2)S antibody or pre-treatment with s elenium, which inhibits PGD(2)S enzymatic activity, both significantly inhi bited the PGD(2)S-induced apoptosis, however, neither had any effect on the apoptosis induced by the known neuronal apoptotic inducer, glutamate. In a ddition, prostaglandins E-1, E-2, and F(2)alpha all inhibited the PGD(2)S-i nduced apoptosis while prostaglandin H-2 had no significant effect. Further more, PGD(2)S isolated from human serum was more effective at inducing apop tosis then recombinantly expressed protein, presumably due to glycosylation . This novel role of PGD2S, as an inducer of apoptosis, may have implicatio ns in PC12 differentiation and possibly some neurological disorders. NeuroR eport 12:2623-2628 (C) 2001 Lippincott Williams & Wilkins.