Nicotinamide prolongs survival of primary cultured hepatocytes without involving loss of hepatocyte-specific functions.
Nicotinamide prolongs survival of primary cultured hepatocytes without involving loss of hepatocyte-specific functions.
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DOI：
10.1016/s0021-9258(18)83650-x
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发表时间：
1989-03
期刊：
影响因子：
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通讯作者：
C. Inoue;H. Yamamoto;T. Nakamura;A. Ichihara;H. Okamoto
中科院分区：
文献类型：
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作者：
C. Inoue;H. Yamamoto;T. Nakamura;A. Ichihara;H. Okamoto
分离的成年大鼠肝细胞在10mM烟酰胺的存在下培养，发现胰岛素和表皮生长因子诱导的DNA合成和细胞增殖被极大地刺激，细胞能够存活一个月以上。在烟酰胺处理的肝细胞中，白蛋白和色氨酸2，3-双加氧酶mRNAs的表达水平明显高于未处理的对照组，并且地塞米松和胰升糖素对色氨酸加氧酶基因表达的诱导作用也被保留。在没有烟酰胺的情况下，原代培养的肝细胞仅存活5-7天，肝细胞特异性表型迅速丧失。烟酰胺处理的肝细胞内NAD水平维持在或高于完整肝脏的水平，但在没有烟酰胺的肝细胞中NAD水平被耗尽。这些结果表明，细胞内NAD水平的维持对肝细胞的生长和功能是必不可少的，烟酰胺可以通过阻止NAD的降解和作为NAD合成的前体来维持NAD水平。
When hepatocytes isolated from adult rats were cultured in the presence of 10 mMnicotinamide, insulin- and epidermal growth factor-induced DNA synthesis and cell proliferation were found to be greatly stimulated, and the cells were able to be kept alive for more than one month. In the nicotinamide-treated hepatocytes, albumin and tryptophan 2,3-dioxygenase mRNAs were present at much higher levels than in the untreated control, and the inducibility of tryptophan oxygenase gene expression by dexamethasone and glucagon was also preserved. Without nicotinamide, primary cultured hepatocytes were viable for only 5–7 days and the hepatocyte-specific phenotypes were rapidly lost. The intracellular NAD level was maintained in the nicotinamide-treated hepatocytes at or above the level in intact liver but depleted in hepatocytes without nicotinamide. These results suggest that the maintenance of the intracellular NAD level is essential for the growth and functioning of hepatocytes and that nicotinamide can preserve the NAD level by blocking NAD degradation as well as by acting as a precursor for NAD synthesis.