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MUCOSAL BIOLOGY

Intestinal ribosomal p70^S6K signaling is increased in piglet rotavirus enteritis

¹Department of Pediatrics, Ochsner Clinic Foundation and Ochsner Children's Research Institute, New Orleans, Louisiana; ²Department of Animal Sciences and ³College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; ⁴Faculty of Nutrition, Texas A&M University, College Station; and ⁵Department of Pediatrics, University of Texas, Houston, Texas

Submitted 10 October 2006 ; accepted in final form 23 November 2006

Recent identification of the mammalian target of rapamycin (mTOR) pathway as an amino acid-sensing mechanism that regulates protein synthesis led us to investigate its role in rotavirus diarrhea. We hypothesized that malnutrition would reduce the jejunal protein synthetic rate and mTOR signaling via its target, ribosomal p70 S6 kinase (p70^S6K). Newborn piglets were artificially fed from birth and infected with porcine rotavirus on day 5 of life. Study groups included infected (fully fed and 50% protein calorie malnourished) and noninfected fully fed controls. Initially, in "worst-case scenario studies," malnourished infected piglets were killed on days 1, 3, 5, and 11 postinoculation, and jejunal samples were compared with controls to determine the time course of injury and p70^S6K activation. Using a 2 x 2 factorial design, we subsequently determined if infection and/or malnutrition affected mTOR activation on day 3. Western blot analysis and immunohistochemistry were used to measure total and phosphorylated p70^S6K; [³H]phenylalanine incorporation was used to measure protein synthesis; and lactase specific activity and villus-crypt dimensions were used to quantify injury. At the peak of diarrhea, the in vitro jejunal protein synthetic rate increased twofold (compared with the rate in the uninfected pig jejunum), concomitant with increased jejunal p70^S6K phosphorylation (4-fold) and an increased p70^S6K level (3-fold, P < 0.05). Malnutrition did not alter the magnitude of p70^S6K activation. Immunolocalization revealed that infection produced a major induction of cytoplasmic p70^S6K and nuclear phospho-p70^S6K, mainly in the crypt. A downregulation of semitendinosus muscle p70^S6K phosphorylation was seen at days 1–3 postinoculation. In conclusion, intestinal activation of p70^S6K was not inhibited by malnutrition but was strongly activated during an active state of mucosal regeneration.

mammalian target of rapamycin; diarrhea; virus; malnutrition

This article has been cited by other articles:

				K. Yao, Y.-L. Yin, W. Chu, Z. Liu, D. Deng, T. Li, R. Huang, J. Zhang, B. Tan, W. Wang, et al. Dietary Arginine Supplementation Increases mTOR Signaling Activity in Skeletal Muscle of Neonatal Pigs J. Nutr., May 1, 2008; 138(5): 867 - 872. [Abstract] [Full Text] [PDF]

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