Regulation of polyamine synthesis and transport by retinoic acid and epidermal growth factor in cultured adult rat type II pneumocytes

During injury of lung epithelial cells, the type II pneumocyte proliferates and differentiates into a type I pneumocyte to restore the epithelium. Pol yamines, which constitute a family of small organic polycations, are requir ed for this process of cell repair. Because retinoic acid (RA) and epiderma l growth factor (EGF) also are involved the purpose of this research was to determine their effect on polyamine transport and synthesis in cultured ty pe II pneumocytes. Rat type II pneumocytes were isolated, cultured overnigh t, and treated with RA and/or EGF far 24 hours. Polyamine transport was det ermined by [H-3]spermidine uptake, and polyamine synthesis was assessed by the activity of the initial rate-limiting enzyme ornithine decarboxylase. E GF (100 ng/mL) significantly increased spermidine transport, but RA did not . At low concentrations of spermidine (2 mu M), the combined effect of RA a nd EGF on spermidine transport was additive. Both EGF (25 ng/mL) and RA (1 mu M) increased polyamine synthesis, and cotreatment resulted in an additiv e effect (a fourfold increase over the control). We also found that ornithi ne decarboxylase activity is greatly diminished in the presence tyrphostin B56, which is a specific inhibitor for the tyrosine kinase of the EGF recep tor, suggesting that polyamine synthesis within the type II pneumocyte may depend on activation of tyrosine kinase of the EGF receptor These results i ndicate that RA and EGF increase the availability of polyamines, which may be important in the lung cell repair process. (J. Nutr. Biochem. 10:518-524 , 1999) (C) Elsevier Science Inc 1999. All rights reserved.