PMID- 17138969
OWN - NLM
STAT- MEDLINE
DCOM- 20070424
LR  - 20211203
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 292
IP  - 3
DP  - 2007 Mar
TI  - Intestinal ribosomal p70(S6K) signaling is increased in piglet rotavirus 
      enteritis.
PG  - G913-22
AB  - 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); [(3)H]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.
FAU - Rhoads, J Marc
AU  - Rhoads JM
AD  - Department of Pediatrics, Ochsner Clinic Foundation and Ochsner Children's 
      Research Institute, New Orleans, Louisiana, USA. j.marc.rhoads@uth.tmc.edu
FAU - Corl, Benjamin A
AU  - Corl BA
FAU - Harrell, Robert
AU  - Harrell R
FAU - Niu, Xiaomei
AU  - Niu X
FAU - Gatlin, Lori
AU  - Gatlin L
FAU - Phillips, Oulayvanh
AU  - Phillips O
FAU - Blikslager, Anthony
AU  - Blikslager A
FAU - Moeser, Adam
AU  - Moeser A
FAU - Wu, Guoyao
AU  - Wu G
FAU - Odle, Jack
AU  - Odle J
LA  - eng
PT  - Journal Article
DEP - 20061130
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Amino Acids)
RN  - 0 (Antigens, Viral)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.2.1.108 (Lactase)
SB  - IM
MH  - Amino Acids/blood
MH  - Animals
MH  - Animals, Newborn
MH  - Antigens, Viral/analysis
MH  - Body Weight
MH  - Diarrhea/metabolism/pathology
MH  - Energy Intake
MH  - Enteritis/blood/*metabolism/virology
MH  - Enterocytes/chemistry/metabolism
MH  - Feces/chemistry
MH  - Intestinal Mucosa/chemistry/metabolism
MH  - Jejunum/chemistry/*metabolism
MH  - Lactase/metabolism
MH  - Malnutrition/metabolism/physiopathology
MH  - Muscle, Skeletal/metabolism
MH  - Muscle, Smooth/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/physiology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/analysis/*metabolism
MH  - Rotavirus Infections/blood/*metabolism
MH  - Signal Transduction/*physiology
MH  - Sus scrofa
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/12/02 09:00
MHDA- 2007/04/25 09:00
CRDT- 2006/12/02 09:00
PHST- 2006/12/02 09:00 [pubmed]
PHST- 2007/04/25 09:00 [medline]
PHST- 2006/12/02 09:00 [entrez]
AID - 00468.2006 [pii]
AID - 10.1152/ajpgi.00468.2006 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G913-22. doi: 
      10.1152/ajpgi.00468.2006. Epub 2006 Nov 30.