Ascorbic acid deficiency affects genes for oxidation-reduction and lipid metabolism in livers from SMP30/GNL knockout mice.
Ascorbic acid deficiency affects genes for oxidation-reduction and lipid metabolism in livers from SMP30/GNL knockout mice.
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DOI：
10.1016/j.bbagen.2014.03.019
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发表时间：
2014-07
期刊：
影响因子：
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通讯作者：
Keita Takahashi;Y. Kishimoto;T. Konishi;Y. Fujita;Masafumi Ito;K. Shimokado;N. Maruyama;A. Ishigami
中科院分区：
文献类型：
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作者：
Keita Takahashi;Y. Kishimoto;T. Konishi;Y. Fujita;Masafumi Ito;K. Shimokado;N. Maruyama;A. Ishigami
背景我们试图阐明抗坏血酸（AA）缺乏对基因表达的影响，因为水溶性抗氧化剂AA是体内重要的生物活性物质。结果我们的微阵列分析显示，AA缺乏增加了与氧化还原过程相关的基因表达，即，类红细胞核因子2（Nrf 2）基因是一种活性氧敏感的转录因子。此外，这种AA缺乏增加了脂质代谢基因的表达，包括细胞色素P450，家族7，亚家族a，多肽1（Cyp 7a 1），这是一个主要的胆汁酸生物合成途径的晚期限制酶。虽然AA缺乏增加Cyp 7a 1蛋白水平，但肝脏和胆囊中的胆汁酸水平下降。由于Cyp 7a 1的活性位点有一个血红素铁，AA必须作为一个还原剂的铁所需的Cyp 7a 1的持续激活。ConclusionsThis实验证据强烈支持AA在生理氧化还原过程中的作用和脂质代谢，包括胆汁酸biosynthes.General意义虽然许多影响AA补充剂已被报道，没有在体内的AA缺乏的微阵列分析。使用这种独特的AA缺陷模型SMP 30/GNL-KO小鼠的结果现在提供了关于以前未知的AA功能的新信息，这些信息将进一步研究AA的体内功能。
BackgroundWe sought to elucidate the effect of an ascorbic acid (AA) deficiency on gene expression, because the water soluble antioxidant AA is an important bioactive substance in vivo.MethodsWe performed microarray analyses of the transcriptome in the liver from senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which are unable to synthesize AA in vivo.ResultsOur microarray analysis revealed that the AA deficiency increased gene expression related to the oxidation–reduction process, i.e., thenuclear factor,erythroid derived 2,like 2(Nrf2) gene, which is a reactive oxygen species-sensitive transcriptional factor. Moreover, this AA deficiency increased the expression of genes for lipid metabolism including thecytochrome P450,family 7,subfamily a,polypeptide1(Cyp7a1), which is a late-limiting enzyme of the primary bile acid biosynthesis pathway. Although an AA deficiency increased the Cyp7a1 protein level, bile acid levels in the liver and gallbladder decreased. Since Cyp7a1 has a heme iron at the active site, AA must function as a reductant of the iron required for the continuous activation of Cyp7a1.ConclusionsThis experimental evidence strongly supports a role for AA in the physiologic oxidation–reduction process and lipid metabolism including bile acid biosynthesis.General significanceAlthough many effects of AA supplementation have been reported, no microarray analysis of AA deficiency in vivo is available. Results from using this unique model of AA deficiency, the SMP30/GNL-KO mouse, now provide new information about formerly unknown AA functions that will implement further study of AA in vivo.