Radiation-induced reductions in transporter mRNA levels parallel reductions in intestinal sugar transport

Abstract

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.

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation

“…Our preliminary measurements of intestinal transport of sugars after a 3-day chronic irradiation with 6.8 Gy (0.094 Gy/h) showed that, unlike our findings for a 7 Gy acute irradiation (5), this absorbed dose did not affect their transport (data not shown). However, increasing the absorbed dose rate to 0.13 and 0.20 Gy/h, and the corresponding absorbed dose to 9.6 and 14.4 Gy, was sufficient to reduce transport of some sugars.…”

“…These studies extend and expand on our earlier studies that investigated reductions in intestinal nutrient transport after acute whole-body exposure to 137 Cs gamma rays and the capacity of a vitamin ACE-enriched diet to protect against these reductions (4, 5). Accordingly, the focus of the current discussion is to compare our findings for chronic versus acute whole-body irradiation.…”

“…The nonmetabolizable glucose analog, 3-O-methylglucose, is absorbed by the same transporter mediating D-glucose uptake, and their comparative uptake rates are often used to distinguish effects on membrane transport from those on glucose metabolism in the cytosol (3). Our studies have shown that transport rates of these nutrients are affected differently when mice are exposed to acute doses of low-LET 137 Cs gamma rays (4, 5). However, the effect of chronic irradiation on nutrient transport is not known and agents to prevent or mitigate such reductions have not been assessed.…”

“…2). These days were selected based on our previous studies, which determined that the nadir for nutrient transport occurs on day 8 after acute irradiation (4, 5). Due to mortality in the day 8 and 10 sacrifice groups, 6 additional mice of similar weight were added to adjust for the decrease in available viable tissues for assay of nutrient transport on day 8 and 10 (total n = 30).…”

Health Risks of Space Exploration: Targeted and Nontargeted Oxidative Injury by High-Charge and High-Energy Particles

“…In addition, the effects of chronic exposure to HZE particles on nutrient absorption, including radioprotectors must be considered. Earlier studies indicated that nutrient absorption in mice was significantly reduced following the exposure to c rays (217,239). Decreases in intestinal sugar absorption were associated with a rapid decrease in SOD and catalase abundance, followed by dramatic upregulation within 4 h and then downregulation a few days later (238).…”