Molecular NeuroscienceProstaglandin D2 synthase induces apoptosis in PC12 neuronal cellsRagolia, Louis1,2, CA; Palaia, Thomas1; Frese, Linda1; Fishbane, Steven1; Maesaka, John K.1,2Author Information 1Department of Medicine, Division of Cell Biology, Winthrop-University Hospital, 222 Station Plaza North, Suite 505-B, Mineola, NY 11501; 2SUNY Medical School at Stony Brook, NY 11794, USA CA,1Corresponding Author and Address Received 10 May 2001; accepted 12 June 2001 Neuroreport: August 28th, 2001 - Volume 12 - Issue 12 - p 2623-2628 Buy SDC Abstract 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 F2α 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. © 2001 Lippincott Williams & Wilkins, Inc.