期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-06088-0
关键词
-
资金
- National Natural Science Foundation of China [31200809]
- Science & Technology Program of Tianjin, China [15ZXLCSY00040]
- Natural Science Foundation of Tianjin City [17JCYBJC25700]
- Open Research Funding Program from the Logistics University of PAP [2015ZXKF09]
Necroptosis, a novel type of programmed cell death, is involved in stroke-induced ischemic brain injury. Although studies have sought to explore the mechanisms of necroptosis, its signaling pathway has not yet to be completely elucidated. Thus, we used oxygen-glucose deprivation (OGD) and middle cerebral artery occlusion (MCAO) models mimicking ischemic stroke (IS) conditions to investigate mechanisms of necroptosis. We found that OGD and MCAO induced cell death, local brain ischemia and neurological deficit, while zVAD-fmk (zVAD, an apoptotic inhibitor), GSK' 872 (a receptor interacting protein kinase-3 (RIP3) inhibitor), and combined treatment alleviated cell death and ischemic brain injury. Moreover, OGD and MCAO upregulated protein expression of the triggers of necroptosis: receptor interacting protein kinase-1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL). The upregulation of these proteins was inhibited by GSK' 872, combination treatments and RIP3 siRNA but not zVAD treatment. Intriguingly, hypoxia-inducible factor-1 alpha (HIF-1 alpha), an important transcriptional factor under hypoxic conditions, was upregulated by OGD and MCAO. Similar to their inhibitory effects on aforementioned proteins upregulation, GSK' 872, combination treatments and RIP3 siRNA decreased HIF-1 alpha protein level. These findings indicate that necroptosis contributes to ischemic brain injury induced by OGD and MCAO and implicate HIF-1 alpha, RIP1, RIP3, and MLKL in necroptosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据