Comparative study of hydrogen peroxide- and 4-hydroxy-2-nonenal-induced cell death in HT22 cells
Comparative study of hydrogen peroxide- and 4-hydroxy-2-nonenal-induced cell death in HT22 cells
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DOI：
10.1016/j.neuint.2007.09.008
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发表时间：
2008-03-01
影响因子：
4.2
通讯作者：
Ito, Yoshihisa
中科院分区：
文献类型：
--
作者：
Ishimura, Atsushi;Ishige, Kumiko;Ito, Yoshihisa
几项研究表明，脂质过氧化反应经常发生在氧化应激反应中，并且当脂质氢过氧化物分解时，形成包括4-羟基-2-壬烯醛（HNE）在内的许多脂质产物。为了阐明氧化应激诱导神经元死亡的机制，在神经系统中，我们研究了H2 O2和HNE诱导的细胞死亡途径在HT 22细胞，小鼠海马细胞系，在相同的实验条件下。用H2 O2和HNE处理以时间和浓度依赖性方式降低这些细胞的活力。在H2 O2处理的细胞中，在核组分中观察到DJ-1和核因子-κ B（NF-κ B）亚基（p65和p50）的免疫反应性显著增加。H_2O_2还可诱导细胞内Ca ~（2+）浓度升高，而Ca_2+通道抑制剂氯化钴（CoCl_2）则可抑制H_2O_2诱导的细胞死亡。在HNE处理的细胞中，没有观察到这些现象;然而，HNE加合物蛋白在暴露于HNE后形成，而不是H2 O2。N-乙酰-L-半胱氨酸（NAC）抑制HNE诱导的细胞死亡和HNE诱导的HNE加合物蛋白的表达，而H2 O2诱导的细胞死亡不受影响。这些结果表明H2 O2诱导的细胞死亡机制与HNE诱导的细胞死亡机制不同，HNE加合蛋白在HNE诱导的细胞死亡中起重要作用。这也表明，在HT 22细胞中H2 O2诱导的细胞死亡的途径不涉及HNE的生产。(C)2007爱思唯尔有限公司保留所有权利。
Several studies have indicated that lipid peroxidation often occurs in response to oxidative stress, and that many aldehydic products including 4-hydroxy-2-nonenal (HNE) are formed when lipid hydroperoxides break down. In order to clarify the mechanism of oxidative stress-induced neuronal death in the nervous system, we investigated H2O2- and HNE-induced cell death pathways in HT22 cells, a mouse hippocampal cell line, under the same experimental conditions. Treatment with H2O2 and HNE decreased the viability of these cells in a time- and concentration-dependent manner. In the cells treated with H2O2, significant increases in the immunoreactivities of DJ-1 and nuclear factor-kappa B (NF-kappa B) subunits (p65 and p50) were observed in the nuclear fraction. H2O2 also induced an increase in the intracellular concentration of Ca2+, and cobalt chloride (CoCl2), a Ca2+ channel inhibitor, suppressed the H2O2-induced cell death. In HNE-treated cells, none of these phenomena were observed; however, HNE adduct proteins were formed after exposure to HNE, but not to H2O2. N-Acetyl-L-Cysteine (NAC) suppressed both HNE-induced cell death and HNE-induced expression of HNE adduct proteins, whereas H2O2-induced cell death was not affected. These findings suggest that the mechanisms of cell death induced by H2O2 different from those induced by HNE in HT22 cells, and that HNE adduct proteins play an important role in HNE-induced cell death. It is also suggested that the pathway for H2O2-induced cell death in HT22 cells does not involve HNE production. (C) 2007 Elsevier Ltd. All rights reserved.