[The role of Src-tyrosine kinases in increasing vascular permeability during experimental ulcerative colitis].
We have shown the increase of Src(Tyr416) phosphorylation in rat colonic mucosa at early stages of 6% iodoacetamide-induced ulcerative colitis (UC), while the level of Src protein expression was not changed. Pretreatment of rats with Src inhibitor PP1 (0.2 mg/100 g, subcutaneously) decreased the colonic vascular permeability (VP) (P < or = 0.001) and pSrc(Tyr416) level during iodoacetamide-UC. Iodoacetamide-induced autophosphorylation and upregulation of VEGFR-2 was associated with Src activation in colonic mucosa of rats. Sequentially, protein-protein interaction between beta-arrestine2 and VE-cadherine was enhanced, that might be a reason of colonic endothelium barrier disruption. We concluded that Src plays a key role in the mechanisms of increasing the colonic VP during experimental UC.
Tolstanova
H M
HM
Khomenko
T A
TA
Ostapchenko
L I
LI
Szabo
S
S
Sandor
Z
Z
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D019390:Arrestins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000503:physiopathology; D003106:Colon / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis; D000071557:beta-Arrestins; D019061:src-Family Kinases / Q000096:biosynthesis / Q000502:physiology*; D000099152:Cadherin 5
D015703:Antigens, CD; D019390:Arrestins; D015820:Cadherins; D040301:Vascular Endothelial Growth Factor Receptor-2; D000071557:beta-Arrestins; D019061:src-Family Kinases; D000099152:Cadherin 5