Kovac Suzana, Anderson Gregory J, Baldwin Graham S
The University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia.
Biochim Biophys Acta. 2011 May;1813(5):889-95. doi: 10.1016/j.bbamcr.2011.02.007. Epub 2011 Feb 12.
The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron deficiency anemia was recognized as a long-term consequence of partial gastrectomy. This review summarizes the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyze the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
肽激素胃泌素已被确认为胃酸分泌的主要调节因子，以及正常和恶性胃肠道细胞的强效促有丝分裂原。50年前，当缺铁性贫血被认为是胃部分切除术后的长期后果时，胃酸在膳食铁吸收中的重要性首次变得明显。这篇综述总结了循环胃泌素、铁状态与结直肠癌之间的联系。胃泌素以微摩尔亲和力结合两个铁离子，对于该激素的非酰胺化形式，铁结合对于体外和体内的生物活性至关重要。通过生化技术证明胃泌素与转铁蛋白之间存在相互作用，从而提出胃泌素催化转铁蛋白与铁的结合。包括以下事实在内的几条证据表明胃泌素可能参与铁稳态：患有铁过载疾病血色素沉着症的小鼠和人类循环胃泌素浓度升高，以及转铁蛋白饱和度与循环胃泌素浓度呈正相关。相反，认识到铁离子在胃泌素的生物活性中发挥意想不到的作用，可能有助于开发针对结直肠癌和胃肠道其他黏膜增殖性疾病的有效疗法。本文是名为“第11届欧洲钙研讨会”的特刊的一部分。
