Blachier F, Robert V, Selamnia M, Mayeur C, Duee P H
Unité d'Ecologie et de Physiologie du Système Digestif, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
FEBS Lett. 1996 Nov 4;396(2-3):315-8. doi: 10.1016/0014-5793(96)01122-2.
In human colon carcinoma HT-29 Glc(-/+) cells, L-arginine is the common precursor of polyamines which are absolutely necessary for cellular proliferation and nitric oxide (NO) with reported anti-proliferative activity. The aim of the present work was to test the effect of the NO donor sodium nitroprusside (SNP) on polyamine synthesis and cellular growth in HT-29 cells. SNP in the micromolar range inhibits cellular putrescine synthesis and this effect is greatly reversed by haemoglobin, supporting the view that the effect of SNP is related to the generation of NO. This corresponds to the inhibition by SNP of ornithine decarboxylase activity. Furthermore, SNP inhibits cellular proliferation. The effect of SNP is reversed by haemoglobin after 2 days of treatment but not after 4 days. Although no acute toxic effect of SNP was detected after 90 min incubation, it greatly enhanced the cellular death rate after several days in culture as estimated by the LDH leakage test. In conclusion, our data raise the possibility of an inhibitory interrelationship between NO and polyamine metabolic pathways. NO induced inhibition of putrescine synthesis and growth in HT-29 cells is discussed from a causal perspective.
在人结肠癌HT - 29 Glc(-/+）细胞中，L - 精氨酸是多胺的共同前体，多胺对于细胞增殖是绝对必需的，而一氧化氮（NO）具有报道的抗增殖活性。本研究的目的是测试NO供体硝普钠（SNP）对HT - 29细胞中多胺合成和细胞生长的影响。微摩尔范围内的SNP抑制细胞腐胺合成，血红蛋白可大大逆转这种作用，这支持了SNP的作用与NO生成有关的观点。这与SNP对鸟氨酸脱羧酶活性的抑制作用相对应。此外，SNP抑制细胞增殖。治疗2天后，血红蛋白可逆转SNP的作用，但4天后则不能。尽管孵育90分钟后未检测到SNP的急性毒性作用，但通过乳酸脱氢酶泄漏试验估计，培养几天后它会大大提高细胞死亡率。总之，我们的数据提出了NO与多胺代谢途径之间存在抑制性相互关系的可能性。从因果关系的角度讨论了NO诱导的HT - 29细胞中腐胺合成和生长的抑制作用。
