VIP down-regulates the inflammatory potential and promotes survival of dying (neural crest-derived) corneal endothelial cells ex vivo: necrosis to apoptosis switch and up-regulation of Bcl-2 and N-cadherin.
VIP down-regulates the inflammatory potential and promotes survival of dying (neural crest-derived) corneal endothelial cells ex vivo: necrosis to apoptosis switch and up-regulation of Bcl-2 and N-cadherin.
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DOI：
10.1111/j.1471-4159.2009.06012.x
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发表时间：
2009-05
影响因子：
4.7
通讯作者：
Abbondandolo CJ
中科院分区：
文献类型：
--
作者：
Koh SW;Cheng J;Dodson RM;Ku CY;Abbondandolo CJ
神经肽VIP分别在免疫系统和神经系统中具有抗炎和保护作用。本研究表明，在角膜内皮（CE）细胞损伤严重的氧化应激（1.4mM H2 O2）在VIP预处理的牛角膜器官培养物中（0、10−10、10−8和10−6 M; 15分钟），以VIP浓度依赖性的方式，将炎症引起的坏死转变为炎症中性的细胞凋亡（显示膜联蛋白V结合、染色质凝聚和DNA片段化）并以VIP拮抗剂（SN）VIPhyb敏感的方式维持ATP水平，同时以激酶A敏感的方式上调抗凋亡Bcl-2和分化标记物N-钙粘蛋白的mRNA水平。结果表明，VIP以浓度依赖和VIP拮抗剂敏感的方式促进CE细胞的长期存活。在VIP预处理后和H2 O2后0.5分钟测量的ATP水平（选择凋亡与坏死的决定因素）分别为39.6±3.3、50.8±6.2、60.1±4.8和53.6±5.3 pmol/μg蛋白（平均值±sem）（p<0.05，ANOVA）。VIP单独处理浓度依赖性地增加N-钙粘蛋白（磷酸化cAMP反应元件结合蛋白）和Bcl-2的水平，而10 −8 M VIP以VIP拮抗剂（SN）VIPhyb敏感的方式增加ATP水平38%（p< 0.02），降低糖原水平32%（p< 0.02）。在CE细胞中表达VPAC 1（而非VPAC 2）受体。因此，CE细胞VIP/VPAC 1信号传导在角膜内皮中既抗炎又保护。
The neuropeptide VIP is anti-inflammatory and protective in the immune and nervous systems, respectively. The present study demonstrated in corneal endothelial (CE) cells injured by severe oxidative stress (1.4mM H2O2) in bovine corneal organ cultures that VIP pre-treatment (0, 10−10, 10−8, and 10−6 M; 15 min), in a VIP concentration-dependent manner, switched the inflammation-causing necrosis to inflammation neutral apoptosis (showing annexin V-binding, chromatin condensation, and DNA fragmentation) and upheld ATP levels in a VIP antagonist (SN)VIPhyb-sensitive manner, while up-regulated mRNA levels of the anti-apoptotic Bcl-2 and the differentiation marker N-cadherin in a kinase A inhibitor-sensitive manner. As a result, VIP, in a concentration-dependent and VIP antagonist-sensitive manners, promoted long-term CE cell survival. ATP levels, a determining factor in the choice of apoptosis vs necrosis, measured after VIP pre-treatment and 0.5 min post- H2O2 were 39.6±3.3, 50.8±6.2, 60.1±4.8, and 53.6±5.3 pmoles/μg protein (mean±sem), respectively (p<0.05, ANOVA). VIP treatment alone concentration-dependently increased levels of N-cadherin, the phosphorylated cAMP-responsive-element binding protein and Bcl-2, while10−8 M VIP, in a VIP antagonist (SN)VIPhyb-sensitive manner, increased ATP level by 38% (p< 0.02) and decreased glycogen level by 32% (p< 0.02). VPAC1 (not VPAC2) receptor was expressed in CE cells. Thus, CE cell VIP/VPAC1 signaling is both anti-inflammatory and protective in the corneal endothelium.
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影响因子：
82.9
作者：
Chen, Chun-Jen;Kono, Hajime;Rock, Kenneth L.
通讯作者：
Rock, Kenneth L.
影响因子：
5.5
作者：
Champattanachai, Voraratt;Marchase, Richard B.;Chatham, John C.
通讯作者：
Chatham, John C.
DOI：
10.1159/000099253
发表时间：
2007-01-01
期刊：
Chemical immunology and allergy
影响因子：
--
作者：
Cursiefen, Claus
通讯作者：
Cursiefen, Claus
影响因子：
3.5
作者：
Fernández, M;Sánchez-Franco, F;Cacicedo, L
通讯作者：
Cacicedo, L
影响因子：
2.5
作者：
Antonawich, FJ;Said, SI
通讯作者：
Said, SI