Ragolia L, Palaia T, Frese L, Fishbane S, Maesaka J K
1Department of Medicine, Division of Cell Biology, Winthrop-University Hospital, 222 Station Plaza North, Suite 505-B, Mineola, NY 11501, USA.
Neuroreport. 2001 Aug 28;12(12):2623-8. doi: 10.1097/00001756-200108280-00008.
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.
神经元细胞凋亡被认为是某些神经疾病的一个病因。在此，我们报告在PC12神经元细胞中，暴露于前列腺素D2合酶（PGD2S）会使细胞凋亡增加5至6倍。通过末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）试验检测到凋亡，且凋亡似乎是通过半胱天冬酶-3激活介导的。用抗PGD2S抗体中和或用抑制PGD2S酶活性的硒预处理，均显著抑制了PGD2S诱导的凋亡，然而，二者对已知的神经元凋亡诱导剂谷氨酸诱导的凋亡均无任何影响。此外，前列腺素E1、E2和F2α均抑制PGD2S诱导的凋亡，而前列腺素H2则无显著作用。此外，从人血清中分离出的PGD2S在诱导凋亡方面比重组表达的蛋白更有效，这可能是由于糖基化所致。PGD2S作为一种凋亡诱导剂的这一新作用，可能对PC12分化以及某些神经疾病有影响。
