Widelitz R B, Matrisian L M, Russell D H, Magun B E
Exp Cell Res. 1984 Nov;155(1):163-70. doi: 10.1016/0014-4827(84)90777-8.
The effects of lysosomotropic amines and polyamines on rat fibroblasts were studied after the administration of epidermal growth factor (EGF) in order to determine whether the intracellular processing of EGF was important for transmission of its biological signal. Following the addition of EGF, cell cultures exhibited a dose-dependent increase in ornithine decarboxylase (ODC) activity. This increase in ODC activity was drastically reduced by both methylamine, a representative lysosomotropic amine, and putrescine, a polyamine precursor. However, inasmuch as methylamine inhibited EGF-induced DNA synthesis by greater than 50%, putrescine had no inhibitory effect. Lysosomotropic amines, but not polyamines, prevented EGF processing as evidenced by their ability to block the release of intracellular 125EGF and by their ability to inhibit the formation of the final intracellular processed product of EGF, as determined by isoelectric focusing. These data suggest that the processing of EGF is consistent with the induction of DNA synthesis and ODC activity. The cellular mechanisms involved in inhibition of ODC induction by polyamines appear to be distinct from those involved in lysosomotropic amines.
为了确定表皮生长因子（EGF）的细胞内加工过程对其生物信号传递是否重要，研究了溶酶体亲和胺和多胺对大鼠成纤维细胞在给予表皮生长因子（EGF）后的影响。添加EGF后，细胞培养物中鸟氨酸脱羧酶（ODC）活性呈剂量依赖性增加。作为代表性溶酶体亲和胺的甲胺和多胺前体腐胺都显著降低了ODC活性的这种增加。然而，由于甲胺抑制EGF诱导的DNA合成超过50%，而腐胺没有抑制作用。溶酶体亲和胺而非多胺阻止了EGF的加工，这可通过它们阻断细胞内125EGF释放的能力以及通过等电聚焦测定的它们抑制EGF最终细胞内加工产物形成的能力来证明。这些数据表明，EGF的加工与DNA合成和ODC活性的诱导是一致的。多胺抑制ODC诱导所涉及的细胞机制似乎与溶酶体亲和胺所涉及的机制不同。
