Protective effects of pituitary adenylate cyclase activating polypeptide in endothelial cells against oxidative stress-induced apoptosis
Protective effects of pituitary adenylate cyclase activating polypeptide in endothelial cells against oxidative stress-induced apoptosis
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DOI：
10.1016/j.ygcen.2006.12.006
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发表时间：
2007-08-01
影响因子：
2.7
通讯作者：
Reglodi, D.
中科院分区：
文献类型：
--
作者：
Racz, B.;Gasz, B.;Reglodi, D.
腺苷酸环化酶激活多肽（PACAP）是一种广泛分布的神经肽，在神经系统和非神经组织中具有多种不同的功能。关于PACAP在内皮细胞中的作用知之甚少。本研究的目的是研究PACAP对氧化应激下内皮细胞存活和凋亡信号通路的影响。将小鼠血管内皮瘤（EOMA）细胞暴露于0.5 mM H2 O2中，MTT试验和流式细胞术检测细胞活力显著降低，凋亡细胞平行增加。与20 nM PACAP 1 -38共孵育增加了细胞活力并降低了凋亡细胞的百分比。流式细胞术分析表明，氧化应激减少了磷酸化的抗凋亡ERK和增加的磷酸化的促凋亡JNK和p38 MAP激酶。PACAP 1 -38处理改善了这些变化：磷酸化ERK水平升高，磷酸化JNK和p38水平降低。所有这些作用都被PACAP拮抗剂PACAP 6 -38同时治疗所消除。总之，我们的研究结果表明，PACAP有效地保护内皮细胞免受氧化应激的凋亡诱导作用。(c)2006年爱思唯尔公司All rights reserved.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has various different functions in the nervous system and in non-neural tissues. Little is known about the effects of PACAP in endothelial cells. The aim of the present study was to investigate the effects of PACAP on endothelial cell survival and apoptotic signaling pathways under oxidative stress. Mouse hemangioendothelioma (EOMA) cells were exposed to 0.5 mM H2O2 which resulted in a marked reduction of cell viability and a parallel increase of apoptotic cells assessed by MTT test and flow cytometry. Co-incubation with 20 nM PACAP1-38 increased cell viability and reduced the percentage of apoptotic cells. Flow cytometry analysis showed that oxidative stress reduced the phosphorylation of the antiapoptotic ERK and increased the phosphorylation of the pro-apoptotic JNK and p38 MAP kinases. PACAP1-38 treatment ameliorated these changes: levels of phospho-ERK were elevated and those of phospho-JNK and p38 were decreased. All these effects were abolished by simultaneous treatment with the PACAP antagonist PACAP6-38. In summary, our results show that PACAP effectively protects endothelial cells against the apoptosis-inducing effects of oxidative stress. (c) 2006 Elsevier Inc. All rights reserved.