Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism.
BACKGROUND
L-Arginine is a nutritional supplement that may be useful for promoting intestinal repair. Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the arginase pathway to yield ornithine and polyamines.


OBJECTIVE
To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis.


METHODS
We determined the effects of arginine on cultured intestinal cell migration, NO production, polyamine levels, and activation of focal adhesion kinase, a key mediator of cell migration.


RESULTS
Arginine increased the rate of cell migration in a dose dependent biphasic manner, and was additive with bovine serum concentrate (BSC). Arginine and an NO donor activated focal adhesion kinase (a tyrosine kinase which localises to cell matrix contacts and mediates beta1 integrin signalling) after wounding. Arginine stimulated cell migration was dependent on focal adhesion kinase (FAK) signalling, as demonstrated using adenovirus mediated transfection with a kinase negative mutant of FAK. Arginine stimulated migration was dependent on NO production and was blocked by NO synthase inhibitors. Arginine dependent migration required synthesis of polyamines but elevating extracellular arginine concentration above 0.4 mM did not enhance cellular polyamine levels.


CONCLUSIONS
These results showed that L-arginine stimulates cell migration through NO and FAK dependent pathways and that combination therapy with arginine and BSC may enhance intestinal restitution via separate and convergent pathways.
Rhoads
J M
JM
Department of Pediatrics, and Center in Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina, USA. mrhoads@ochsner.org
Chen
W
W
Gookin
J
J
Wu
G Y
GY
Fu
Q
Q
Blikslager
A T
AT
Rippe
R A
RA
Argenzio
R A
RA
Cance
W G
WG
Weaver
E M
EM
Romer
L H
LH
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases; D009569:Nitric Oxide / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000502:physiology; D065108:Ornithine Decarboxylase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011073:Polyamines / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D013552:Swine; D014162:Transfection; D014443:Tyrosine / Q000502:physiology
D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D009569:Nitric Oxide; D014443:Tyrosine; D001120:Arginine; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D009955:Ornithine Decarboxylase