Dudeja P K, Dahiya R, Brasitus T A
Biochim Biophys Acta. 1986 Dec 16;863(2):309-12. doi: 10.1016/0005-2736(86)90272-5.
Recently, our laboratory, utilizing the 1,2-dimethylhydrazine model of colonic adenocarcinoma, demonstrated alterations in the 'dynamic component' of fluidity in brush-border membranes prepared from distal colonocytes of rats administered this agent for 5, 10 and 15 weeks, i.e., before the development of colon cancer. Furthermore, changes in the sphingomyelin content and sphingomyelin/phosphatidylcholine molar ratio of these membranes appeared, at least partially, to be responsible for these fluidity alterations. In an attempt to elucidate the mechanism(s) involved in these dimethylhydrazine-induced lipid changes, in the present studies the activities of sphingomyelin synthetase and magnesium-dependent neutral sphingomyelinase, enzymes involved in the synthesis and degradation of this phospholipid, respectively, were examined and compared in distal colonic brush-border membranes prepared from rats after 5, 10 or 15 weeks administration of dimethylhydrazine or diluent. The results of these studies demonstrate that alterations in both these enzymatic activities can be detected after administration of dimethylhydrazine and appear to, at least in part, be responsible for the changes in membrane sphingomyelin composition noted previously. These results as well as a discussion of their possible serve as the basis for the present report.
最近，我们的实验室利用1,2 - 二甲基肼诱导的结肠腺癌模型，发现在给大鼠连续5周、10周和15周（即在结肠癌发生之前）注射该试剂后，从远端结肠细胞制备的刷状缘膜流动性的“动态成分”发生了改变。此外，这些膜中鞘磷脂含量和鞘磷脂/磷脂酰胆碱摩尔比的变化似乎至少部分地导致了这些流动性改变。为了阐明这些二甲基肼诱导的脂质变化所涉及的机制，在本研究中，我们检测并比较了在给大鼠注射二甲基肼或稀释剂5周、10周或15周后，从远端结肠刷状缘膜中提取的鞘磷脂合成酶和镁依赖性中性鞘磷脂酶的活性，这两种酶分别参与该磷脂的合成和降解。这些研究结果表明，注射二甲基肼后可检测到这两种酶活性的改变，并且这些改变似乎至少部分地导致了之前所观察到的膜鞘磷脂组成的变化。这些结果以及对其可能影响的讨论构成了本报告的基础。
