Heger R J, Baybutt R C
Department of Foods and Nutrition, Kansas State University, Manhattan, KS 66506-1407, USA.
J Nutr Biochem. 1999 Sep;10(9):518-24. doi: 10.1016/s0955-2863(99)00038-8.
During injury of lung epithelial cells, the type II pneumocyte proliferates and differentiates into a type I pneumocyte to restore the epithelium. Polyamines, which constitute a family of small organic polycations, are required for this process of cell repair. Because retinoic acid (RA) and epidermal growth factor (EGF) also are involved, the purpose of this research was to determine their effect on polyamine transport and synthesis in cultured type II pneumocytes. Rat type II pneumocytes were isolated, cultured overnight, and treated with RA and/or EGF for 24 hours. Polyamine transport was determined by [(3)H]spermidine uptake, and polyamine synthesis was assessed by the activity of the initial rate-limiting enzyme ornithine decarboxylase. EGF (100 ng/mL) significantly increased spermidine transport, but RA did not. At low concentrations of spermidine (2 microM), the combined effect of RA and EGF on spermidine transport was additive. Both EGF (25 ng/mL) and RA (1 microM) increased polyamine synthesis, and cotreatment resulted in an additive effect (a fourfold increase over the control). We also found that ornithine decarboxylase activity is greatly diminished in the presence of tyrphostin B56, which is a specific inhibitor for the tyrosine kinase of the EGF receptor, suggesting that polyamine synthesis within the type II pneumocyte may depend on activation of tyrosine kinase of the EGF receptor. These results indicate that RA and EGF increase the availability of polyamines, which may be important in the lung cell repair process.
在肺上皮细胞损伤期间，II型肺细胞增殖并分化为I型肺细胞以修复上皮。多胺是一类小的有机聚阳离子家族，该细胞修复过程需要多胺参与。由于视黄酸（RA）和表皮生长因子（EGF）也参与其中，本研究的目的是确定它们对培养的II型肺细胞中多胺转运和合成的影响。分离大鼠II型肺细胞，过夜培养，并用RA和/或EGF处理24小时。通过[³H]亚精胺摄取测定多胺转运，通过初始限速酶鸟氨酸脱羧酶的活性评估多胺合成。EGF（100 ng/mL）显著增加亚精胺转运，但RA没有。在低浓度亚精胺（2 μM）时，RA和EGF对亚精胺转运的联合作用是相加的。EGF（25 ng/mL）和RA（1 μM）均增加多胺合成，联合处理产生相加效应（比对照增加四倍）。我们还发现，在酪氨酸磷酸化酶抑制剂B56存在下，鸟氨酸脱羧酶活性大大降低，酪氨酸磷酸化酶抑制剂B56是EGF受体酪氨酸激酶的特异性抑制剂，这表明II型肺细胞内的多胺合成可能依赖于EGF受体酪氨酸激酶的激活。这些结果表明，RA和EGF增加了多胺的可用性，这在肺细胞修复过程中可能很重要。
