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首页> 外文期刊>The Journal of Nutritional Biochemistry >Casein phosphopeptides modulate proliferation and apoptosis in HT-29 cell line through their interaction with voltage-operated L-type calcium channels.
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Casein phosphopeptides modulate proliferation and apoptosis in HT-29 cell line through their interaction with voltage-operated L-type calcium channels.

机译：酪蛋白磷酸肽通过与电压操作的L型钙通道相互作用来调节HT-29细胞系的增殖和凋亡。

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At the intestinal level, proliferation and apoptosis are modulated by the extracellular calcium concentration; thus, dietary calcium may exert a chemoprotective role on normal differentiated intestinal cells, while it may behave as a carcinogenesis promoter in transformed cells. Calcium in milk is associated with casein and casein phosphopeptides (CPPs), hence is preserved from precipitation. CPPs were demonstrated to induce uptake of extracellular calcium ions by in vitro intestinal tumor HT-29 cells but only upon differentiation. Here, the hypothesis that CPPs could differently affect proliferation and apoptosis in undifferentiated and differentiated HT-29 cells through their binding with calcium ions was investigated. Results showed that CPPs protect differentiated intestinal cells from calcium overload toxicity and prevent their apoptosis favoring proliferation while inducing apoptosis in undifferentiated tumor cells. The CPP effect on undifferentiated HT-29 cells, similar to that exerted by ethyleneglycol-O, O'-bis(2-aminoethyl)-N, N, N', N'-tetraacetic acid (EGTA), is presumably due to the ability in binding the extracellular calcium. The effect on differentiated HT-29 cells is coupled to the interaction of CPPs with the voltage-operated L-type calcium channels, known to activate calcium entry into the cells under depolarization and to exert a mitogenic effect: the use of an agonist potentiates the cell response to CPPs, while the antagonists abolish the response to CPPs (36% of examined cells) or reduce both the percentage of responsive cells and the increase of intracellular calcium concentration. Taken together, these results confirm the potentialities of CPPs as nutraceuticals/functional food and also as modulators of cellular processes connected to the expression of a cancer phenotype
机译：在肠一级，细胞外钙浓度调节增殖和凋亡。因此，饮食中的钙可能对正常分化的肠细胞发挥化学保护作用，而在转化的细胞中它可能充当致癌促进剂。牛奶中的钙与酪蛋白和酪蛋白磷酸肽（CPP）有关，因此可以防止沉淀。已证明CPPs可以通过体外肠肿瘤HT-29细胞诱导胞外钙离子的摄取，但仅在分化时才如此。在此，研究了CPPs通过与钙离子结合可以不同地影响未分化和分化的HT-29细胞增殖和凋亡的假说。结果表明，CPPs保护分化的肠细胞免受钙超载毒性的侵害，并防止其凋亡促进增殖，同时诱导未分化的肿瘤细胞凋亡。推测CPP对未分化HT-29细胞的作用类似于乙二醇-O，O'-双（2-氨基乙基）-N，N，N'，N'-四乙酸（EGTA）所产生的作用。结合细胞外钙的能力。对分化的HT-29细胞的作用与CPP与电压操纵的L型钙通道的相互作用有关，已知该L型钙通道可激活钙在去极化下进入细胞并产生有丝分裂作用：使用激动剂可增强钙离子的产生。细胞对CPPs的反应，而拮抗剂则取消了对CPPs的反应（占检测细胞的36％），或者降低了反应细胞的百分比和细胞内钙浓度的增加。综上所述，这些结果证实了CPP作为营养食品/功能食品以及与癌症表型表达相关的细胞过程调节剂的潜力。

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