首页> 外文期刊>American Journal of Physiology >Precursor peptide progastrin(1-80) reduces apoptosis of intestinal epithelial cells and upregulates cytochrome c oxidase Vb levels and synthesis of ATP.
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Precursor peptide progastrin(1-80) reduces apoptosis of intestinal epithelial cells and upregulates cytochrome c oxidase Vb levels and synthesis of ATP.

机译:前体肽前胃泌素(1-80)减少肠上皮细胞的凋亡,并上调细胞色素c氧化酶Vb的水平和ATP的合成。

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We recently reported that downregulation of gastrin gene expression in colon cancer cells significantly suppresses relative levels of mitochondrial cytochrome c (cyt c) oxidase Vb (Cox Vb) RNA and protein. These unexpected findings suggested the possibility that gastrin gene products [mainly progastrin (PG)] may be directly or indirectly mediating the observed effects in colon cancer cells. Because colon cancer cells do not respond to exogenous PG, we examined the possibility of whether PG regulates Cox Vb expression in gastrin-responsive intestinal epithelial cells (IECs) in vitro. Levels of Cox Vb RNA and protein were significantly increased in a dose-dependent manner in response to PG. Mitochondrial synthesis of ATP was also increased by approximately three- to fivefold in response to optimal concentrations (0.1-1.0 nm) of PG. Possible antiapoptotic effects of PG were additionally examined, because activation of caspases 9 and 3 had been noted in colon cancer cells downregulated for gastrin gene expression. We measured a significant loss in the levels of cyt c in the cytosol of PG-treated vs. control IEC cells, which correlated with a significant loss in the activation of caspases 9 and 3, resulting in a significant loss in DNA fragmentation on PG treatment of the cells. Our results thus suggest the novel possibility that the precursor PG peptide exerts direct antiapoptotic effects on IECs, which may contribute to the observed growth effects of PG on these cells. Additionally, Cox Vb gene appears to be an important intracellular target of PG, resulting in an increase in ATP levels, which may also contribute to the observed increase in the growth of target cells in response to PG.
机译:我们最近报道说,结肠癌细胞中胃泌素基因表达的下调显着抑制了线粒体细胞色素c(cyt c)氧化酶Vb(Cox Vb)RNA和蛋白质的相对水平。这些出乎意料的发现表明,胃泌素基因产物[主要是前胃泌素(PG)]可能直接或间接介导结肠癌细胞中观察到的作用。因为结肠癌细胞对外源性PG不响应,所以我们检查了PG是否在体外调节胃泌素反应性肠上皮细胞(IEC)中Cox Vb表达的可能性。响应PG,Cox Vb RNA和蛋白质的水平以剂量依赖性方式显着增加。响应最佳浓度(0.1-1.0 nm)PG,ATP的线粒体合成也增加了大约三到五倍。另外检查了PG可能的抗凋亡作用,因为已经在针对胃泌素基因表达下调的结肠癌细胞中注意到了胱天蛋白酶9和3的激活。我们测量了PG处理的vs.对照IEC细胞的胞浆中cyt c水平的显着降低,这与胱天蛋白酶9和3激活的显着降低相关,从而导致PG处理中DNA片段的显着丧失的细胞。因此,我们的结果表明前体PG肽对IEC具有直接抗凋亡作用的新可能性,这可能有助于观察到PG在这些细胞上的生长作用。此外,Cox Vb基因似乎是PG的重要细胞内靶标,导致ATP水平升高,这也可能有助于观察到响应PG的靶细胞生长增加。

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