Lactase decline in weaning rats is regulated at the transcriptional level and not caused by termination of milk ingestion
Lactase decline in weaning rats is regulated at the transcriptional level and not caused by termination of milk ingestion
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DOI：
10.1093/jn/127.9.1737
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发表时间：
1997-09-01
影响因子：
4.2
通讯作者：
Sakuma, K
中科院分区：
文献类型：
--
作者：
Motohashi, Y;Fukushima, A;Sakuma, K
大鼠出生后发育过程中乳糖酶活性下降，但人们对这种现象的潜在分子机制知之甚少。我们试图澄清这种调节是在转录水平还是转录后水平，并检查饮食因素对该调节的影响。新生大鼠在第21天分为两组，即长期哺乳组和断奶组。长期哺乳组大鼠再哺乳6天，而断奶组大鼠与母鼠分开并在同一时期饲喂未净化的饲料。分别通过蛋白质印迹和北方印迹分析确定断奶期间乳糖酶蛋白和mRNA浓度下降的模式，并与乳糖酶活性进行比较。它们之间存在显着的相关性 (P < 0.001)：比活性与蛋白质的关系为 r = 0.97，比活性与 mRNA 的关系为 r = 0.99，蛋白质与 mRNA 的关系为 r = 0.96。每毫克 DNA 的乳糖酶活性显示出与比活性相似的模式。这一结果反驳了乳糖酶活性下降是由于断奶期间新合成材料稀释造成的，并表明转录调控。此外，长期哺乳的大鼠在乳糖酶蛋白、mRNA、比活性和每毫克 DNA 活性方面显示出与断奶仔鼠相同的结果。这些观察结果表明，乳糖酶表达的调节是在转录水平上，并且不受牛奶摄入终止的影响。
Lactase activity declines during postnatal development in rats, but little is known about the underlying molecular mechanism of this phenomenon. We attempted to clarify whether the regulation was at the transcriptional or post-transcriptional level and to examine the effects of dietary factors on that regulation. Newborn rats were divided into two groups, prolonged nursing and weaning, at d 21. The prolonged nursing rats were nursed for a further 6 d, whereas weaning rats were separated from their dams and fed nonpurified diet for the same period. The patterns of declining lactase protein and mRNA concentrations during weaning were determined by Western blot and Northern blot analyses, respectively, and compared with lactase activity. There were significant (P < 0.001) correlations between them: r = 0.97 for specific activity vs. protein, r = 0.99 for specific activity vs. mRNA and r = 0.96 for protein vs. mRNA. The lactase activity per milligram DNA showed a pattern similar to that of the specific activity. This result argues against the decline in lactase activity being due to the dilution caused by newly synthesized materials during the weaning period and suggests transcriptional regulation. Furthermore, the prolonged nursing rats showed the same results as weanlings for lactase protein, mRNA, specific activity and activity per milligram DNA. These observations indicate that the regulation of lactase expression is at the transcriptional level and that it is not affected by the termination of milk ingestion.