Rj. Heger et Rc. Baybutt, Regulation of polyamine synthesis and transport by retinoic acid and epidermal growth factor in cultured adult rat type II pneumocytes, J NUTR BIOC, 10(9), 1999, pp. 518-524
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.