Analysis of signaling pathway of novel lipid hydroperoxide dependent cell death

磷脂氢过氧化物谷胱甘肽过氧化物酶（PHGPx）是一种细胞内的抗氧化酶，直接减少过氧化的磷脂从我们的组织特异性PHGPx基因敲除小鼠的分析，我们澄清，PHGPx的消耗可以诱导新的细胞死亡，通过在几个组织中产生磷脂氢过氧化物。这种新的脂质过氧化氢依赖性细胞死亡可以通过添加维生素E完全抑制。为了阐明新的细胞死亡途径的机制，我们使用他莫昔芬诱导的PHGPx敲除MEF细胞筛选化学文库和shRNA文库。我们发现了六种抑制剂和大约20个抑制新的脂质过氧化氢依赖性细胞死亡的基因，敲除抑制剂的靶基因可以抑制新的细胞死亡。这些基因与调控细胞凋亡、坏死性凋亡和自噬性细胞死亡的基因没有区别。这些结果意味着脂质过氧化氢依赖性细胞死亡是一种新的程序性细胞死亡。

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids From analysis of our tissue-specific PHGPx knockout mice, we clarified that depletion of PHGPx can induce novel cell death via generation of phospholipid hydroperoxide in several tissues. This novel lipid hydroperoxide dependent cell death can be completely suppressed by addition of vitamin E. To clarify the mechanism of novel cell death pathway, we screened chemical library and shRNA library using tamoxifen inducible PHGPx knockout MEF cells. We found six inhibitors and about 20 genes to suppress the novel lipid hydroperoxide dependent cell death.Knockdown of target genes against inhibitors can be suppressed novel cell death. These identified genes were not different from that regulating apoptosis, necroptosis and autophagic cell death. These results means that lipid hydroperoxide dependent cell death is novel programmed cell death.