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Group IB secretory phospholipase A 2 induces neuronal cell death via apoptosis
Author(s) -
Yagami Tatsurou,
Ueda Keiichi,
Asakura Kenji,
HayasakiKajiwara Yoko,
Nakazato Hitoshi,
Sakaeda Toshiyuki,
Hata Satoshi,
Kuroda Takayuki,
Takasu Nobuo,
Hori Yozo
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00800.x
Subject(s) - programmed cell death , apoptosis , biology , microbiology and biotechnology , phospholipase a2 , eicosanoid , prostaglandin d2 , cyclooxygenase , arachidonic acid , neurotoxicity , cell , receptor , biochemistry , medicine , enzyme , toxicity
Group IB secretory phospholipase A 2 (sPLA 2 ‐IB) mediates cell proliferation, cell migration, hormone release and eicosanoid production via its receptor in peripheral tissues. In the CNS, high‐affinity binding sites of sPLA 2 ‐IB have been documented. However, it remains obscure whether sPLA 2 ‐IB causes biologic or pathologic response in the CNS. To this end, we examined effects of sPLA 2 ‐IB on neuronal survival in primary cultures of rat cortical neurons. sPLA 2 ‐IB induced neuronal cell death in a concentration‐dependent manner. This death was a delayed response requiring a latent time for 6 h; sPLA 2 ‐IB‐induced neuronal cell death was accompanied with apoptotic blebbing, condensed chromatin, and fragmented DNA, exhibiting apoptotic features. Before cell death, sPLA 2 ‐IB liberated arachidonic acid (AA) and generated prostaglandin D 2 (PGD 2 ) from neurons. PGD 2 and its metabolite, Δ12‐PGJ 2 , exhibited neurotoxicity. Inhibitors of sPLA 2 and cyclooxygenase‐2 (COX‐2) significantly suppressed not only AA release, but also PGD 2 generation. These inhibitors significantly prevented neurons from sPLA 2 ‐IB‐induced neuronal cell death. In conclusion, we demonstrate a novel biological response, apoptosis, of sPLA 2 ‐IB in the CNS. Furthermore, the present study suggests that PGD 2 metabolites, especially Δ12‐PGJ 2 , might mediate sPLA 2 ‐IB‐induced apoptosis.