<br>Chemerin 通过 ChemR23/CAMKK2/AMPK 通路逆转新生儿缺氧缺血性脑病的神经损伤并改善神经元凋亡。,Cell Death & Disease

当前位置： X-MOL 学术 › Cell Death Dis. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Chemerin 通过 ChemR23/CAMKK2/AMPK 通路逆转新生儿缺氧缺血性脑病的神经损伤并改善神经元凋亡。
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-02-04 , DOI: 10.1038/s41419-019-1374-y
Yixin Zhang _{1,

2} , Ningbo Xu ₂ , Yan Ding ₂ , Desislava Met Doycheva ₂ , Yiting Zhang ₂ , Qian Li ₂ , Jerry Flores ₂ , Mina Haghighiabyaneh ₂ , Jiping Tang ₂ , John H Zhang _{2,

3}

Affiliation

缺氧缺血性脑病（HIE）是一种破坏性的神经系统事件，会导致婴儿的长期神经发育后果。专注于减弱半暗带神经元凋亡的治疗策略似乎很有希望。鉴于脂肪因子在 HIE 中的神经保护作用日益得到认可，我们在 HIE 实验模型中研究了脂肪因子新成员 Chemerin 的潜在抗凋亡作用。在本研究中，10天大的幼鼠接受右颈总动脉结扎，然后缺氧2.5小时。缺氧后1小时，给幼崽鼻内施用人重组凯莫瑞（rh-凯莫瑞）。在这里，我们发现 rh-chemerin 可以防止神经元凋亡和变性，这可以通过促凋亡标记物、裂解的 caspase 3 和 Bax 的表达减少以及 Fluoro-Jade C 和 TUNEL 阳性神经元的数量来证明。此外，rh-Chemerin 逆转了新生大鼠 HIE 后 24 小时和 4 周由缺氧缺血引起的神经和形态学损伤。此外，凯莫瑞介导的神经元存活与凯莫瑞受体 23 (chemR23)、磷酸化钙调蛋白依赖性蛋白激酶激酶 2 (CAMKK2) 以及磷酸化单磷酸腺苷激活蛋白激酶 (AMPK) 的升高相关。 HIE后24小时，对chemR23、CAMKK2和AMPK的特异性抑制消除了rh-chemerin的抗凋亡作用，表明rh-chemerin部分通过激活chemR23/CAMKK2/AMPK信号通路改善神经元凋亡。神经元凋亡是 HIE 后病理变化和神经功能损伤的一个公认的促成因素。这些结果揭示了 rh-chemerin 的神经保护机制，并表明 chemR23 的激活可用于防止 HIE 中的神经元凋亡。

"点击查看英文标题和摘要"

Chemerin reverses neurological impairments and ameliorates neuronal apoptosis through ChemR23/CAMKK2/AMPK pathway in neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a devastating neurological event that contributes to the prolonged neurodevelopmental consequences in infants. Therapeutic strategies focused on attenuating neuronal apoptosis in the penumbra appears to be promising. Given the increasingly recognized neuroprotective roles of adipokines in HIE, we investigated the potential anti-apoptotic roles of a novel member of adipokines, Chemerin, in an experimental model of HIE. In the present study, 10-day-old rat pups underwent right common carotid artery ligation followed by 2.5 h hypoxia. At 1 h post hypoxia, pups were intranasally administered with human recombinant chemerin (rh-chemerin). Here, we showed that rh-chemerin prevented the neuronal apoptosis and degeneration as evidenced by the decreased expression of the pro-apoptotic markers, cleaved caspase 3 and Bax, as well as the numbers of Fluoro-Jade C and TUNEL-positive neurons. Furthermore, rh-Chemerin reversed neurological and morphological impairments induced by hypoxia-ischemia in neonatal rats at 24 h and 4 weeks after HIE. In addition, chemerin-mediated neuronal survival correlated with the elevation of chemerin receptor 23 (chemR23), phosphorylated calmodulin-dependent protein kinase kinase 2 (CAMKK2), as well as phosphorylated adenosine monophosphate-activated protein kinase (AMPK). Specific inhibition of chemR23, CAMKK2, and AMPK abolished the anti-apoptotic effects of rh-chemerin at 24 h after HIE, demonstrating that rh-chemerin ameliorated neuronal apoptosis partially via activating chemR23/CAMKK2/AMPK signaling pathway. Neuronal apoptosis is a well-established contributing factor of pathological changes and the neurological impairment after HIE. These results revealed mechanisms of neuroprotection by rh-chemerin, and indicated that activation of chemR23 might be harnessed to protect from neuronal apoptosis in HIE.

更新日期：2019-02-05

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南