PMID- 22361732
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20220311
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 302
IP  - 9
DP  - 2012 May 1
TI  - L-arginine uptake by cationic amino acid transporter 2 is essential for colonic 
      epithelial cell restitution.
PG  - G1061-73
LID - 10.1152/ajpgi.00544.2011 [doi]
AB  - Restoration of the colonic epithelial barrier is an important response during 
      colitis. L-arginine (L-Arg) is a semiessential amino acid that reduces murine 
      colitis induced by Citrobacter rodentium. Cationic amino acid transporter (CAT) 
      proteins increase L-Arg uptake into cells. L-Arg is utilized to produce nitric 
      oxide (NO), by inducible NO synthase (iNOS), or L-ornithine (L-Orn) by arginase 
      (Arg) enzymes. The latter is followed by generation of polyamines by ornithine 
      decarboxylase (ODC) and L-proline (L-Pro) by ornithine aminotransferase (OAT). We 
      show that L-Arg enhanced epithelial restitution in conditionally immortalized 
      young adult mouse colon (YAMC) cells in a wound repair model, and in isolated 
      mouse colonic epithelial cells (CECs), using a cell migration assay. Restitution 
      was impaired by C. rodentium. Wounding induced CAT2, and inhibition of L-Arg 
      uptake by the competitive inhibitor L-lysine (L-Lys) or by CAT2 shRNA, but not 
      CAT1 shRNA, decreased restitution. Migration was impaired in CECs treated with 
      L-Lys or from CAT2(-/-) mice. Wounding increased Arg1 expression, and inhibition 
      of arginase with S-(2-boronoethyl)-L-cysteine (BEC) or Arg1 shRNA inhibited 
      restitution in YAMC cells; cell migration in CECs was also impaired by BEC. 
      Inhibition of ODC or iNOS did not alter restitution. L-Orn or L-Pro restored 
      restitution in cells treated with BEC or Arg1 shRNA, whereas the polyamine 
      putrescine had no benefit. Wounding increased OAT levels, OAT shRNA inhibited 
      restitution, and L-Pro restored restitution in cells with OAT knockdown. Uptake 
      of L-Arg, and its metabolism by Arg1 to L-Orn and conversion to L-Pro by OAT is 
      essential for colonic epithelial wound repair.
FAU - Singh, Kshipra
AU  - Singh K
AD  - Department of Medicine, Division of Gastroenterology, Vanderbilt University 
      Medical Center, Nashville, Tennessee 37232, USA.
FAU - Coburn, Lori A
AU  - Coburn LA
FAU - Barry, Daniel P
AU  - Barry DP
FAU - Boucher, Jean-Luc
AU  - Boucher JL
FAU - Chaturvedi, Rupesh
AU  - Chaturvedi R
FAU - Wilson, Keith T
AU  - Wilson KT
LA  - eng
GR  - P01-CA-028842/CA/NCI NIH HHS/United States
GR  - R01 DK053620/DK/NIDDK NIH HHS/United States
GR  - R01-DK-053620/DK/NIDDK NIH HHS/United States
GR  - P01-CA-116087/CA/NCI NIH HHS/United States
GR  - I01 BX001453/BX/BLRD VA/United States
GR  - R01-AT-004821/AT/NCCIH NIH HHS/United States
GR  - 3R01-AT-004821S1/AT/NCCIH NIH HHS/United States
GR  - P30-DK-058404/DK/NIDDK NIH HHS/United States
GR  - R01 AT004821/AT/NCCIH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120223
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Cationic Amino Acid Transporter 2)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Animals
MH  - Arginine/administration & dosage/*pharmacokinetics
MH  - Cationic Amino Acid Transporter 2/*metabolism
MH  - Colitis/*drug therapy/*metabolism
MH  - Colon
MH  - Epithelial Cells/drug effects/*metabolism
MH  - Intestinal Mucosa/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC3362080
EDAT- 2012/03/01 06:00
MHDA- 2012/06/26 06:00
PMCR- 2013/05/01
CRDT- 2012/02/25 06:00
PHST- 2012/02/25 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - ajpgi.00544.2011 [pii]
AID - GI-00544-2011 [pii]
AID - 10.1152/ajpgi.00544.2011 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2012 May 1;302(9):G1061-73. doi: 
      10.1152/ajpgi.00544.2011. Epub 2012 Feb 23.