15d-Prostaglandin J2 Enhancement of Nerve Growth Factor-Induced Neurite Outgrowth Is Blocked by the Chemoattractant Receptor-Homologous Molecule Expressed on T-Helper Type 2 Cells (CRTH2) Antagonist CAY10471 in PC12 Cells
15d-Prostaglandin J2 Enhancement of Nerve Growth Factor-Induced Neurite Outgrowth Is Blocked by the Chemoattractant Receptor-Homologous Molecule Expressed on T-Helper Type 2 Cells (CRTH2) Antagonist CAY10471 in PC12 Cells
复制标题
DOI：
10.1254/jphs.10001sc
复制
发表时间：
2010-05-01
影响因子：
3.5
通讯作者：
Baba, Akemichi
中科院分区：
文献类型：
--
作者：
Hatanaka, Michiyoshi;Shibata, Norihiro;Baba, Akemichi
在t -辅助性2型细胞（CRTH2）上表达的趋化受体同源分子是最近发现的PGD(2)和15-脱氧- δ (12,14)-PGJ(2) （15d-PGJ(2)）的前列腺素（PG）受体。我们研究了15d-PGJ(2)促进神经生长因子（NGF）诱导的PC12细胞神经突生长的机制。CAY10471 （CRTH2拮抗剂）抑制15d-PGJ诱导的神经突促进和p38丝裂原活化蛋白（MAP）激酶磷酸化(2)。相比之下，13,14-二氢-15-酮- pgd (2) (DK-PGD(2))（选择性CRTH2激动剂）刺激其磷酸化，但未能产生神经突促进作用。这些结果首次表明，15d-PGJ(2)的作用是由CRTH2介导的，尽管单独激活CRTH2不足以发挥潜在的作用。
The chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2) is the most recently identified prostaglandin (PG) receptor for both PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We examined the mechanism by which 15d-PGJ(2) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. CAY10471 (CRTH2 antagonist) inhibited both the neurite-promotion and p38 mitogen-activated protein (MAP) kinase phosphorylation induced by 15d-PGJ(2). In contrast, 13,14-dihydro-15-keto-PGD(2) (DK-PGD(2)) (selective CRTH2 agonist) stimulated its phosphorylation but failed to produce neurite-promoting effects. These suggest, for the first time, the action of 15d-PGJ(2) is mediated by CRTH2, although the CRTH2 activation alone is insufficient for the underlying action.