Gastrins, iron and colorectal cancer.
Gastrins, iron and colorectal cancer.
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DOI：
10.1039/b909112m
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
G. Baldwin
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文献类型：
--
作者：
G. Baldwin
这篇小综述探讨了循环胃泌素，铁状态和结直肠癌之间的联系。肽激素胃泌素是酸分泌的主要调节剂，也是正常和恶性胃肠道细胞的有效促分裂剂。胃泌素以μM的亲和力结合两个铁离子，并且在激素的非酰胺化形式的情况下，铁结合对于生物活性是必需的。铁离子配体已被鉴定为18个氨基酸的肽甘氨酸延伸的胃泌素中的谷氨酸7、8和9。胃泌素和转铁蛋白之间的相互作用首先通过共价交联技术得到证实，最近又通过表面等离子体共振得到证实。因此，我们提出，胃泌素作为催化剂在负载铁的转铁蛋白。最近的一些证据，包括事实上，循环胃泌素的浓度增加，在小鼠和人类与铁超载疾病血色病，转铁蛋白饱和度与循环胃泌素浓度呈正相关，表明胃泌素可能参与铁稳态。此外，认识到铁离子可能在非酰胺化胃泌素的生物活性中发挥意想不到的作用，可能有助于开发结肠直肠癌的新疗法。
This minireview explores the connections between circulating gastrins, iron status and colorectal cancer. The peptide hormone gastrin is a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. Gastrins bind two ferric ions with μM affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity. The ferric ion ligands have been identified as glutamates 7, 8 and 9 in the 18 amino acid peptide glycine-extended gastrin. An interaction between gastrin and transferrin was first demonstrated by covalent crosslinking techniques, and has been recently confirmed by surface plasmon resonance. We have therefore proposed that gastrins act as catalysts in the loading of transferrin with iron. Several recent lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease haemochromatosis, and that transferrin saturation positively correlates with circulating gastrin concentrations, suggest that gastrins may be involved in iron homeostasis. In addition the recognition that ferric ions may play an unexpected role in the biological activity of non-amidated gastrins may assist in the development of new therapies for colorectal carcinoma.