Younoszai M K, Parekh V V, Stephen T C, Hoffman J L
Department of Pediatrics, University of Louisville, Kentucky 40292, USA.
Proc Soc Exp Biol Med. 1996 Apr;211(4):339-45. doi: 10.3181/00379727-211-43978.
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.
我们的目的是研究青春期大鼠体内空肠黏膜中鸟氨酸脱羧酶和酪氨酸激酶在增殖过程中的关系。此前尚未有关于它们在体内条件下增殖性肠黏膜中关系的报道。根据体外研究结果推测，在结肠黏膜增殖过程中酪氨酸激酶活性调节鸟氨酸脱羧酶活性（马宗达AP。《美国生理学杂志》259：G626 - G630，1990）。1型糖尿病诱导空肠黏膜增生，而在对照大鼠和糖尿病大鼠中，二氟甲基鸟氨酸给药均可抑制增生。在诱导糖尿病3天、6天和10天后测定空肠黏膜重量和酶活性，诱导糖尿病10天后测定酪氨酸特异性磷酸化蛋白。在6天和10天的研究期后，二氟甲基鸟氨酸抑制了空肠黏膜增殖和酪氨酸激酶活性。在3天的研究期后，尽管空肠黏膜生长受到抑制，但酪氨酸激酶活性未受影响。在对照大鼠和糖尿病大鼠的所有时间段，酪氨酸激酶和鸟氨酸脱羧酶的活性均高度显著相关。在对照大鼠和糖尿病大鼠的空肠黏膜中均观察到34、54、80和200 kDa蛋白的酪氨酸特异性磷酸化。在二氟甲基鸟氨酸处理的大鼠中，上述蛋白的磷酸化可忽略不计，而14 kDa蛋白的磷酸化则很明显。我们推测，在体内鸟氨酸脱羧酶活性可能调节酪氨酸激酶活性，并且在二氟甲基鸟氨酸处理的大鼠中，14 kDa蛋白的磷酸化与黏膜生长受抑制有关。
