Nutrients regulate the colonic vitamin D system in mice:: Relevance for human colon malignancy
Nutrients regulate the colonic vitamin D system in mice:: Relevance for human colon malignancy
复制标题
DOI：
10.1093/jn/136.3.561
复制
发表时间：
2006-03-01
影响因子：
4.2
通讯作者：
Kállay, E
中科院分区：
文献类型：
--
作者：
Cross, HS;Lipkin, M;Kállay, E
二羟基胆钙化醇结合其受体作为一种有效的抗有丝分裂，促分化，促凋亡激素在不同的细胞类型和组织。流行病学研究表明，人血清中维生素D前体羟基胆钙化醇浓度低与结直肠癌发病率有关。我们已经证明了在人类结直肠组织和细胞中，前体转化为二羟基胆钙化醇，以及维生素D分解代谢途径的存在。这些发现表明结肠维生素D系统在肿瘤预防中的作用。低钙摄入量已被发现与人类结直肠癌的发病率有关。在喂食相当于人类低摄入量钙的小鼠中，降解维生素D途径增加，主要是在升结肠中。重新喂养小鼠高水平的维生素D和钙降低了组织25-羟基胆钙化醇24-羟化酶的活性，但只有补充叶酸才能完全正常化降解途径的表达。正常化也发生在低钙饮食的小鼠被喂食大豆或植物雌激素染料木黄酮。这些结果表明，结肠维生素D的合成不仅是严格控制的营养钙，但也叶酸，甲基供体，这表明表观遗传控制的维生素D羟化酶。
Dihydroxycholecalciferol bound to its receptor functions as a potent antimitotic, prodifferentiating, proapoptotic hormone in different cell types and tissues. Epidemiological studies have linked low human serum concentrations of the vitamin D precursor hydroxycholecalciferol to colorectal cancer incidence. We have demonstrated in human colorectal tissue and cells the conversion of the precursor to dihydroxycholecalciferol, as well as the existence of the vitamin D catabolic pathway. These findings suggest a role for the colonic vitamin D system in tumor prevention. Low calcium intake has been found to be associated with human colorectal cancer incidence. In mice fed calcium equivalent to a low human intake, the degradative vitamin D pathway was increased, mainly in the ascending colon. Refeeding the mice high levels of vitamin D and calcium lowered tissue 25-hydroxycholecalciferol 24-hydroxylase activity, but only replenishment of folic acid normalized expression of the degradative pathway completely. Normalization occurred also when mice consuming low calcium diets were fed soy or the phytoestrogen genistein. These results indicate that colonic vitamin D synthesis is not only under stringent control of nutritional calcium, but also of folate, a methyl donor, which suggests epigenetic control of vitamin D hydroxylases.