Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, P.R. China.
Food Funct. 2018 Mar 1;9(3):1878-1888. doi: 10.1039/c7fo01040k. Epub 2018 Mar 12.
A cationic peroxidase (POD) was purified from proso millet seeds (PmPOD) using ammonium sulfate fractionation, cation exchange, and size exclusion chromatography. The purified PmPOD showed toxicity to normal cells and tumor cells, but was more sensitive in HT29 cells. Furthermore, the mechanism driving HCT116 and HT29 cell death by PmPOD was the induction of receptor interacting protein kinase 1 (RIPK1)- and RIPK3-dependent necroptosis, independent of apoptosis. More importantly, PmPOD could induce tumor necrosis factor-α (TNF-α) production through transcriptional upregulation. In addition, PmPOD could restore RIPK3 expression in HCT116 cells via the demethylation of the RIPK3 genomic sequence. Taken together, these results suggest that two distinct mechanisms are involved in PmPOD-induced necroptosis: the autocrine production of TNF-α and the restoration of RIPK3 expression.
一种阳离子过氧化物酶（POD）从黍米种子（PmPOD）中通过硫酸铵分级、阳离子交换和分子筛层析进行纯化。纯化的 PmPOD 对正常细胞和肿瘤细胞具有毒性，但对 HT29 细胞更敏感。此外，PmPOD 通过诱导受体相互作用蛋白激酶 1（RIPK1）和 RIPK3 依赖性坏死，而不是凋亡，导致 HCT116 和 HT29 细胞死亡。更重要的是，PmPOD 可以通过转录上调诱导肿瘤坏死因子-α（TNF-α）的产生。此外，PmPOD 可以通过 RIPK3 基因组序列的去甲基化恢复 HCT116 细胞中 RIPK3 的表达。总之，这些结果表明，PmPOD 诱导的坏死涉及两种不同的机制：TNF-α 的自分泌产生和 RIPK3 表达的恢复。
