军事医学2017，Vol.41Issue(1)：25-32,8.DOI:10.7644/j.issn.1674-9960.2017.01.007
PI3 K在肿瘤坏死因子诱导L929细胞程序性坏死过程中的调控作用研究
Identification of role of PI3K in mediating necroptosis of L929 cells induced by tumor necrosis factor alpha
摘要
Abstract
Objective To identify the role of phosphatidylinositol-3-kinase(PI3K) in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) and the involved mechanism.Methods Knockdown of p110α,receptor-interacting protein 1(RIP1) or both p110αand RIP1 was mediated by the specific short hairpin RNA (shRNA) lentivirus and verified by RT-PCR or Western blotting .In addition , Western blotting was used to detect phosphorylation of mixed lineage kinase domain-like protein(MLKL) and protein kinase B(AKT) or tetramerization of MLKL.Cell death was measured by micros-copy and flow cytometry.Results AKT phosphorylation and TNFα-induced necroptosis of L929 cells were suppressed by the inhibitors of PI3K or AKT, as well as p110αknockdown.Moreover, RIP1 knockdown did not inhibit L929 cell death induced by TNFαplus Z-VAD, but the RIP1-independent necroptosis was inhibited by p 110αknockdown.In addition, p110αknockdown suppressed MLKL phosphorylation and tetramerization induced by TNFαwith Z-VAD in L929 cells. Conclusion PI3K mediates necroptosis of L929 cells induced by TNFαby activating AKT and MLKL, respectively.关键词
磷脂酰肌醇3-激酶/肿瘤坏死因子α/细胞程序性坏死/蛋白激酶B/混合系激酶区域样蛋白Key words
phosphatidylinositol-3-kinase/tumor necrosis factor alpha/necroptosis/protein kinase B/MLKL分类
生物科学引用本文复制引用
常喜喜,陈国柱,胡世平,王宇,王丽丽,武帅,王籽橙,杜芝燕,于继云,张毅..PI3 K在肿瘤坏死因子诱导L929细胞程序性坏死过程中的调控作用研究[J].军事医学,2017,41(1):25-32,8.基金项目
国家自然科学基金资助项目（31201041）；国家重大科技专项重大新药创制资助项目 （）
