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 D-2 synthase (PGD(2)S) 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-PGD(2)S antibody or pre-treatment with selenium, which inhibits PGD(2)S enzymatic activity, both significantly inhibited the PGD(2)S-induced apoptosis, however, neither had any effect on the apoptosis induced by the known neuronal apoptotic inducer, glutamate. In addition, prostaglandins E-1, E-2, and F(2)alpha all inhibited the PGD(2)S-induced apoptosis while prostaglandin H-2 had no significant effect. Furthermore, PGD(2)S 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. NeuroReport 12:2623-2628 (C) 2001 Lippincott Williams & Wilkins.