2022年4月30日 · In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death.

2021年1月4日 · Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus...

2017年7月18日 · Activation of the pseudokinase mixed lineage kinase domain-like (MLKL) upon its phosphorylation by the protein kinase RIPK3 triggers necroptosis, a form of programmed cell death in which rupture of cellular membranes yields release of intracellular components.

在这里，我们发现用zVAD治疗小鼠可以显着降低脂多糖（LPS）攻击后的死亡率并减轻疾病。 值得注意的是，在LPS攻击的小鼠中，zVAD治疗还可以通过促进坏死性坏死和抑制巨噬细胞的促炎反应来降低腹膜巨噬细胞的百分比。 体外研究表明，zVAD预处理可促进LPS诱导的一氧化氮介导的骨髓巨噬细胞（BMDMs）坏死性坏死，从而降低促炎性细胞因子的分泌。 有趣的是，在内毒素休克的小鼠模型中，zVAD治疗促进了髓样抑制细胞（MDSC）的积累，并且该过程抑制了巨噬 …

2016年3月4日 · In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate...

2023年9月9日 · 本研究基于老药新用的研究策略，对FDA批准上市的药物库进行筛选，发现抗癌药物维罗非尼可以作为一种有效的程序性坏死抑制剂。 通过直接结合受体相互作用蛋白激酶1（RIPK1），维罗非尼可以有效抑制RIPK1激酶活性，阻碍坏死小体的形成和下游信号传导，从而抑制细胞程序性坏死（图1）。 图1维罗非尼抑制TNFα诱导的程序性坏死机制图. 分子动力学模拟揭示了维罗非尼与RIPK1的结合模式。...

2021年1月4日 · Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus positioning ZBP1 as an effector of cell death in the context of bacterial blockade of pro-inflammatory signaling.

2019年8月2日 · Here, we found that treatment of mice with zVAD could significantly reduce mortality and alleviate disease after lipopolysaccharide (LPS) challenge. Notably, in LPS-challenged mice, treatment with zVAD could also reduce the percentage of peritoneal macrophages by promoting necroptosis and inhibiting pro …

目的:探讨脂多糖 (LPS)联合z-VAD-FMK介导M1亚型巨噬细胞程序性坏死的机制.方法:使用佛波酯 (PMA)和干扰素γ (IFN-γ)诱导THP-1细胞系分化得到M0和M1亚型巨噬细胞.以LPS (100μg/L)分别处理M0和M1巨噬细胞,检测不同时点的乳酸脱氢酶释放和DNA断裂情况,并观察不同抑制剂的影响.采用Western blot法检测受体相互作用蛋白 (RIP)1,RIP3,细胞外信号调节激酶 (ERK),c-Jun氨基末端激酶 (JNK),P38和NOD样受体蛋白3 (NLRP3)的蛋白水平.结果:LPS能够诱导M1亚型巨噬细胞发 …

2023年8月24日 · Previous studies have revealed that lipopolysaccharide (LPS) can induce necroptosis of intraperitoneal macrophages in the presence of z-VAD, whereas genetic inactivation or pharmacological ...