title: 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.
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, NJ, USA.
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Roche
authors.forename: Prasad V S V
authors.initials: PV
authors.lastname: Neti
authors.forename: Francis W
authors.initials: FW
authors.lastname: Kemp
authors.forename: Amit
authors.initials: A
authors.lastname: Agrawal
authors.forename: Alicia
authors.initials: A
authors.lastname: Attanasio
authors.forename: Véronique
authors.initials: V
authors.lastname: Douard
authors.forename: Anjali
authors.initials: A
authors.lastname: Muduli
authors.forename: Edouard I
authors.initials: EI
authors.lastname: Azzam
authors.forename: Edward
authors.initials: E
authors.lastname: Norkus
authors.forename: Michael
authors.initials: M
authors.lastname: Brimacombe
authors.forename: Roger W
authors.initials: RW
authors.lastname: Howell
authors.forename: Ronaldo P
authors.initials: RP
authors.lastname: Ferraris
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D001835:Body Weight / Q000502:physiology; D019587:Dietary Supplements; D004307:Dose-Response Relationship, Radiation; D005632:Fructose / Q000378:metabolism*; D005720:Gamma Rays; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism* / Q000528:radiation effects; D051296:Glucose Transporter Type 5; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism* / Q000528:radiation effects; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D051246:Glucose Transport Proteins, Facilitative; D051296:Glucose Transporter Type 5; D012333:RNA, Messenger; C465351:Slc2a5 protein, mouse; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D014801:Vitamin A; D005632:Fructose; D005947:Glucose