Relation of ornithine decarboxylase and tyrosine kinase activity in the jejunal mucosa in vivo.
Our aim was to study the relationship between jejunal mucosal activity of ornithine decarboxylase and tyrosine kinase during proliferation in adolescent rats in vivo. Their relationship in the proliferating intestinal mucosa under in vivo conditions has not been reported before. From the results of in vitro studies, it was speculated that tyrosine kinase activity modulated ornithine decarboxylase activity during colonic mucosal proliferation (Majumdar AP. Am J Physiol 259:G626-G630, 1990). Jejunal mucosal hyperplasia was induced by Type 1 diabetes and suppressed in both control and diabetic rats by administration of difluoromethylornithine. Jejunal mucosal weight and enzyme activity were determined after 3, 6, and 10 days, and tyrosine-specific phosphorylated proteins after 10 days of induction of diabetes. Difluoromethylornithine suppressed jejunal mucosal proliferation and tyrosine kinase activity after the 6- and 10- day study periods. After the 3-day study period although jejunal mucosal growth was suppressed, tyrosine kinase activity was not. Activity of tyrosine kinase and ornithine decarboxylase were highly significantly correlated at all time periods in both control and diabetic rats. Tyrosine-specific phosphorylated proteins of 34, 54, 80, and 200 kDa proteins were observed in jejunal mucosa of both control and diabetic rats. In the difluoromethylornithine-treated rats, phosphorylation of the above proteins was negligible while the phosphorylation of a 14-kDa protein was prominent. We speculate that in vivo ornithine decarboxylase activity may be modulating tyrosine kinase activity and that phosphorylation of a 14-kDa protein was associated with suppressed mucosal growth in difluoromethylornithine-treated rats.
Younoszai
M K
MK
Department of Pediatrics, University of Louisville, Kentucky 40292, USA.
Parekh
V V
VV
Stephen
T C
TC
Hoffman
J L
JL
D000818:Animals; D001835:Body Weight; D004247:DNA / Q000032:analysis; D003921:Diabetes Mellitus, Experimental; D004326:Drinking; D004435:Eating; D000518:Eflornithine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006965:Hyperplasia / Q000139:chemically induced; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D007583:Jejunum / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000378:metabolism
D011506:Proteins; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases; D009955:Ornithine Decarboxylase; D000518:Eflornithine