Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Kuopio, PL 1627, 70211 Kuopio, Finland.
Amino Acids. 2010 Feb;38(2):575-81. doi: 10.1007/s00726-009-0418-5. Epub 2009 Dec 3.
The role of polyamines in carbon tetrachloride (CCl(4))-induced organ injury was studied in syngenic rats and transgenic rats with activated polyamine catabolism. In syngenic rats, administration of CCl(4) resulted in the induction of hepatic spermidine/spermine N(1)-acetyltransferase (SSAT), accumulation of putrescine, reduction in spermine level and appearance of moderate hepatic injury within 24 h. Upon treatment with CCl(4), transgenic rats overexpressing SSAT displayed induction of both hepatic and pancreatic SSAT, with subsequent accumulation of putrescine and decrease of both spermidine and spermine pools. Administration of CCl(4) in SSAT transgenic rats induced not only massive hepatic injury, but also severe acute necrotizing pancreatitis. Pretreatment of the animals with catabolically stable functional polyamine mimetic, alpha-methylspermidine (MeSpd) prevented pancreatic and hepatic injury in SSAT rats and markedly reduced liver damage in syngenic animals. As assessed by immunostaining of proliferating cell nuclear antigen, MeSpd increased the amount of regenerating hepatocytes in both genotypes. These results show that CCl(4) induces hepatic and pancreatic polyamine catabolism, and the extent of organ damage correlates with the degree of polyamine depletion. Furthermore, MeSpd protects against CCl(4)-induced hepatic and pancreatic damage and promotes tissue regeneration.
研究了多胺在四氯化碳（CCl4）诱导的器官损伤中的作用，研究对象为具有激活多胺分解代谢的同基因大鼠和转基因大鼠。在同基因大鼠中，CCl4 的给药导致肝亚精胺/精脒 N1-乙酰基转移酶（SSAT）的诱导、腐胺的积累、精脒水平的降低以及 24 小时内出现中度肝损伤。在用 CCl4 处理时，过表达 SSAT 的转基因大鼠显示肝和胰腺 SSAT 的诱导，随后腐胺积累，精脒和精脒池减少。在 SSAT 转基因大鼠中给予 CCl4 不仅诱导了大量的肝损伤，还诱导了严重的急性坏死性胰腺炎。用代谢稳定的功能性多胺模拟物α-甲基精脒（MeSpd）预处理动物可预防 SSAT 大鼠的胰腺和肝损伤，并显著降低同基因动物的肝损伤。通过增殖细胞核抗原的免疫染色评估，MeSpd 增加了两种基因型中再生肝细胞的数量。这些结果表明，CCl4 诱导肝和胰腺多胺分解代谢，器官损伤的程度与多胺耗竭的程度相关。此外，MeSpd 可预防 CCl4 诱导的肝和胰腺损伤并促进组织再生。
