Department of Pharmacology and Physiology, New Jersey Medical School, NJ, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Jan;298(1):R173-82. doi: 10.1152/ajpregu.00612.2009. Epub 2009 Nov 11.
More than a century ago, ionizing radiation was observed to damage the radiosensitive small intestine. Although a large number of studies has since shown that radiation reduces rates of intestinal digestion and absorption of nutrients, no study has determined whether radiation affects mRNA expression and dietary regulation of nutrient transporters. Since radiation generates free radicals and disrupts DNA replication, we tested the hypotheses that at doses known to reduce sugar absorption, radiation decreases the mRNA abundance of sugar transporters SGLT1 and GLUT5, prevents substrate regulation of sugar transporter expression, and causes reductions in sugar absorption that can be prevented by consumption of the antioxidant vitamin A, previously shown by us to radioprotect the testes. Mice were acutely irradiated with (137)Cs gamma rays at doses of 0, 7, 8.5, or 10 Gy over the whole body. Mice were fed with vitamin A-supplemented diet (100x the control diet) for 5 days prior to irradiation after which the diet was continued until death. Intestinal sugar transport was studied at days 2, 5, 8, and 14 postirradiation. By day 8, d-glucose uptake decreased by approximately 10-20% and d-fructose uptake by 25-85%. With increasing radiation dose, the quantity of heterogeneous nuclear RNA increased for both transporters, whereas mRNA levels decreased, paralleling reductions in transport. Enterocytes of mice fed the vitamin A supplement had > or = 6-fold retinol concentrations than those of mice fed control diets, confirming considerable intestinal vitamin A uptake. However, vitamin A supplementation had no effect on clinical or transport parameters and afforded no protection against radiation-induced changes in intestinal sugar transport. Radiation markedly reduced GLUT5 activity and mRNA abundance, but high-d-fructose diets enhanced GLUT5 activity and mRNA expression in both unirradiated and irradiated mice. In conclusion, the effect of radiation may be posttranscriptional, and radiation-damaged intestines can still respond to dietary stimuli.
一个多世纪以前，人们观察到电离辐射会损伤敏感的小肠。尽管此后大量研究表明辐射会降低肠道对营养物质的消化和吸收速率，但没有研究确定辐射是否会影响营养物质转运体的 mRNA 表达和膳食调节。由于辐射会产生自由基并破坏 DNA 复制，我们检验了以下假设：在已知会降低糖吸收的剂量下，辐射会降低糖转运体 SGLT1 和 GLUT5 的 mRNA 丰度，阻止底物对糖转运体表达的调节，并导致糖吸收减少，而我们之前的研究表明，抗氧化维生素 A 可预防这种减少，维生素 A 先前被证明可保护睾丸免受辐射。用（137）Cs γ射线全身照射小鼠，剂量分别为 0、7、8.5 或 10 Gy。照射前 5 天，用添加维生素 A 的饮食（对照饮食的 100 倍）喂养小鼠，照射后继续用这种饮食喂养直至小鼠死亡。照射后第 2、5、8 和 14 天研究肠道糖转运。第 8 天，d-葡萄糖摄取减少约 10-20%，d-果糖摄取减少 25-85%。随着辐射剂量的增加，两种转运体的异质核 RNA 量增加，而 mRNA 水平降低，与转运减少平行。用维生素 A 补充剂喂养的小鼠的肠细胞中的视黄醇浓度比用对照饮食喂养的小鼠高 > 或 = 6 倍，证实了肠道中维生素 A 的大量摄取。然而，维生素 A 补充剂对临床或转运参数没有影响，也不能预防辐射引起的肠道糖转运变化。辐射显著降低 GLUT5 活性和 mRNA 丰度，但高 d-果糖饮食增强了未受辐射和受辐射的小鼠的 GLUT5 活性和 mRNA 表达。总之，辐射的影响可能是转录后发生的，并且辐射损伤的肠道仍能对膳食刺激做出反应。
