1. Radiation-induced reductions in transporter mRNA levels parallel reductions in intestinal sugar transport
- Author
-
Michael Brimacombe, Roger W. Howell, Edouard I. Azzam, Anjali Muduli, Francis W. Kemp, Ronaldo P. Ferraris, Alicia Attanasio, Edward Norkus, Marjolaine Roche, Amit Agrawal, Veronique Douard, Prasad V.S.V. Neti, Department of Pharmacology and Physiology, Drexel University College of Medicine, School Cancer Center - Department of Radiology, Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Department of Preventive Medicine and Community Health - New Jersey Medical School, Our Lady of Mercy Medical Center, National Institute of Allergy and Infectious Diseases RC1-AI-078518, National Science Foundation IOS-0722365, National Institute of Diabetes and Digestive and Kidney Diseases, and DK-075617A National Cancer Institute RO1-CA-83838
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Ratón ,[SDV]Life Sciences [q-bio] ,Glucose Transport Proteins, Facilitative ,Fructose ,Biology ,medicine.disease_cause ,Antioxidants ,Ionizing radiation ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Sodium-Glucose Transporter 1 ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Intestine, Small ,medicine ,Animals ,RNA, Messenger ,Vitamin A ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Glucose Transporter Type 5 ,Body Weight ,Biological Transport ,Dose-Response Relationship, Radiation ,Transporter ,Articles ,Small intestine ,Glucose ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Gamma Rays ,030220 oncology & carcinogenesis ,Dietary Supplements ,Models, Animal ,biology.protein ,GLUT5 ,Oxidative stress - 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 with137Cs gamma rays at doses of 0, 7, 8.5, or 10 Gy over the whole body. Mice were fed with vitamin A-supplemented diet (100× 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 ∼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 ≥ 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.
- Published
- 2010
- Full Text
- View/download PDF