胆汁酸
细胞凋亡
程序性细胞死亡
细胞毒性T细胞
生物化学
细胞毒性
细胞生物学
CYP27A1
生物
氧化应激
肠上皮
化学
上皮
体外
遗传学
作者
Juan I. Barrasa,Nieves Olmo,M.A. Lizarbe,Javier Turnay
标识
DOI:10.1016/j.tiv.2012.12.020
摘要
Bile acids are natural detergents mainly involved in facilitating the absorption of dietary fat in the intestine. In addition to this absorptive function, bile acids are also essential in the maintenance of the intestinal epithelium homeostasis. To accomplish this regulatory function, bile acids may induce programmed cell death fostering the renewal of the epithelium. Here we first discuss on the different molecular pathways of cell death focusing on apoptosis in colon epithelial cells. Bile acids may induce apoptosis in colonocytes through different mechanisms. In contrast to hepatocytes, the extrinsic apoptotic pathway seems to have a low relevance regarding bile acid cytotoxicity in the colon. On the contrary, these molecules mainly trigger apoptosis through direct or indirect mitochondrial perturbations, where oxidative stress plays a key role. In addition, bile acids may also act as regulatory molecules involved in different cell signaling pathways in colon cells. On the other hand, there is increasing evidence that the continuous exposure to certain hydrophobic bile acids, due to a fat-rich diet or pathological conditions, may induce oxidative DNA damage that, in turn, may lead to colorectal carcinogenesis as a consequence of the appearance of cell populations resistant to bile acid-induced apoptosis. Finally, some bile acids, such as UDCA, or low concentrations of hydrophobic bile acids, can protect colon cells against apoptosis induced by high concentrations of cytotoxic bile acids, suggesting a dual behavior of these agents as pro-death or pro-survival molecules.
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