Prostaglandin D2 toxicity in primary neurons is mediated through its bioactive cyclopentenone metabolites.
Prostaglandin D2 toxicity in primary neurons is mediated through its bioactive cyclopentenone metabolites.
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DOI：
10.1016/j.neuro.2013.08.001
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发表时间：
2013-12
期刊：
影响因子：
3.4
通讯作者：
Graham, Steven H.
中科院分区：
文献类型：
--
作者：
Liu, Hao;Li, Wenjin;Rose, Marie E.;Pascoe, Jordan L.;Miller, Tricia M.;Ahmad, Muzamil;Poloyac, Samuel M.;Hickey, Robert W.;Graham, Steven H.
关键词：
前列腺素D2 （PGD2）是脑内最丰富的前列腺素，但其对神经元细胞死亡的影响是复杂的，尚未完全了解。PGD2可能通过激活DP受体或代谢成环五烯酮前列腺素（CyPGs） PGJ2， Δ12-PGJ2和15-脱氧-Δ12,14-PGJ2来调节神经元细胞死亡，而不依赖于前列腺素受体而诱导细胞死亡。本研究旨在阐明PGD2在神经元细胞死亡中的作用及其潜在机制。在浓度≥10 μM的大鼠原代神经元富集培养物中，PGD2剂量依赖性诱导细胞死亡，DP1或DP2受体拮抗剂均不能逆转这种效应。抗氧化剂n -乙酰半胱氨酸（NAC）和谷胱甘肽含有巯基，可与cypg结合，但不能与抗坏血酸或生育酚结合，可减轻pgd2诱导的细胞死亡。在神经元培养液中检测PGD2向CyPGs的转化；单独使用这些CyPG代谢物治疗显示出与PGD2相似的效果，包括凋亡神经元细胞死亡和泛素化蛋白的积累。破坏脂钙素型前列腺素D合成酶（L-PGDS）可保护神经元免受缺氧。这些结果支持了PGD2通过其生物活性CyPG代谢物而不是DP受体激活在原代神经元培养中引发细胞毒性作用的假设。
Prostaglandin D2 (PGD2) is the most abundant prostaglandin in brain but its effect on neuronal cell death is complex and not completely understood. PGD2 may modulate neuronal cell death via activation of DP receptors or its metabolism to the cyclopentenone prostaglandins (CyPGs) PGJ2, Δ12-PGJ2 and 15-deoxy-Δ12,14-PGJ2, inducing cell death independently of prostaglandin receptors. This study aims to elucidate the effect of PGD2 on neuronal cell death and its underlying mechanisms. PGD2 dose-dependently induced cell death in rat primary neuron-enriched cultures in concentrations of ≥ 10 μM, and this effect was not reversed by treatment with either DP1 or DP2 receptor antagonists. Antioxidants N-acetylcysteine (NAC) and glutathione which contain sulfhydryl groups that can bind to CyPGs, but not ascorbate or tocopherol, attenuated PGD2-induced cell death. Conversion of PGD2 to CyPGs was detected in neuronal culture medium; treatment with these CyPG metabolites alone exhibited effects similar to those of PGD2, including apoptotic neuronal cell death and accumulation of ubiquitinated proteins. Disruption of lipocalin-type prostaglandin D synthase (L-PGDS) protected neurons against hypoxia. These results support the hypothesis that PGD2 elicits its cytotoxic effects through its bioactive CyPG metabolites rather than DP receptor activation in primary neuronal culture.
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影响因子：
6.1
作者：
Liu, Hao;Li, Wenjin;Ahmad, Muzamil;Miller, Tricia M.;Rose, Marie E.;Poloyac, Samuel M.;Uechi, Guy;Balasubramani, Manimalha;Hickey, Robert W.;Graham, Steven H.
通讯作者：
Graham, Steven H.
影响因子：
11.2
作者：
AUER, RN;SIESJO, BK
通讯作者：
SIESJO, BK
DOI：
10.1152/ajpendo.00274.2006
发表时间：
2007-04-01
影响因子：
5.1
作者：
Chambers, Kari T.;Weber, Sarah M.;Corbett, John A.
通讯作者：
Corbett, John A.
影响因子：
2.9
作者：
ABDELHALIM, MS;LUNDEN, I;ANGGARD, E
通讯作者：
ANGGARD, E
影响因子：
7.3
作者：
Crider, JY;Griffin, BW;Sharif, NA
通讯作者：
Sharif, NA