Hemin protects against oxygen-glucose deprivation-induced apoptosis activation via neuroglobin in SH-SY5Y cells
Hemin protects against oxygen-glucose deprivation-induced apoptosis activation via neuroglobin in SH-SY5Y cells
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氯化血红素通过 SH-SY5Y 细胞中的神经红蛋白防止氧-葡萄糖剥夺诱导的细胞凋亡激活
DOI：
10.1007/s11064-017-2230-z
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Li-Na Zhang
中科院分区：
文献类型：
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作者：
Yun-Jia Wang;Qian-Yi Peng;Song-yun Deng;Cai-Xia Chen;Long Wu;Li Hunag;Li-Na Zhang
本研究旨在探讨氯高铁血红素对氧糖剥夺（OGD）处理的神经元的神经保护作用的机制。该研究使用 OGD 处理的 SH-SY5Y 细胞（人神经母细胞瘤细胞）。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定评估 SH-SY5Y 细胞的细胞活力，并通过流式细胞术分析细胞凋亡率，使用膜联蛋白 V-异硫氰酸荧光素和碘化丙啶染色，有或没有氯高铁红素预处理。给予氯化血红素并结合神经球蛋白 (Nqb)、硫氧还蛋白-1、过氧还蛋白-2 或血红素加氧酶-1 siRNA 瞬时转染后，检测细胞活力和凋亡激活。用氯化血红素预处理检测线粒体释放细胞色素 c 以及 Ngb 和细胞色素 c 之间的相互作用。 Hemin 对 OGD 处理的 SH-SY5Y 细胞具有神经保护作用，该作用主要是通过上调 Ngb 介导的。此外，氯高铁血红素诱导的 Ngb 表达通过促进 Ngb 与线粒体中细胞色素 c 的相互作用来抑制线粒体释放细胞色素 c。目前的研究结果为血红素的神经保护机制提供了新的见解。结论是低剂量氯化血红素预处理通过抑制细胞凋亡对 OGD 处理的 SH-SY5Y 细胞具有神经保护作用。氯化血红素对缺氧缺血性神经元损伤后的神经保护作用主要由 Ngb 介导。一种潜在机制是氯化血红素诱导的线粒体 Ngb 过度表达，它通过与细胞色素 c 的结合抑制内源性细胞凋亡。
This study aimed to investigate the mechanism underlying the neuroprotective effect of hemin in oxygen–glucose deprivation (OGD)-treated neurons. OGD-treated SH-SY5Y cells (human neuroblastoma cells) were used in the study. The cellular viability of SH-SY5Y cells was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the cell apoptosis rate was determined by flow cytometry analysis with Annexin V-fluorescein isothiocyanate and propidium iodide staining with or without hemin pretreatment. Cell viability and apoptotic activation were detected after hemin administration combined with neuroglobin (Nqb), thioredoxin-1, peroxiredoxin-2, or heme oxygenase-1 siRNA transient transfection. The release of cytochrome c from mitochondria and the interaction between Ngb and cytochrome c were examined with hemin pretreatment. Hemin had a neuroprotective effect in OGD-treated SH-SY5Y cells, which was mainly mediated by the upregulation of Ngb. Moreover, the release of cytochrome c from mitochondria was inhibited by hemin-induced Ngb expression through facilitating the interaction of Ngb with cytochrome c in mitochondria. The present findings provided new insights into the neuroprotective mechanisms of hemin. It was concluded that low-dose hemin pretreatment had a neuroprotective effect in OGD-treated SH-SY5Y cells, through inhibiting cell apoptosis. The neuroprotective effects of hemin following hypoxic–ischemic neuronal damage were mainly mediated by Ngb. One underlying mechanism was hemin-induced overexpression of mitochondrial Ngb, which inhibited endogenous apoptosis via the association with cytochrome c.