Ascorbic acid deficiency affects genes for oxidation-reduction and lipid metabolism in livers from SMP30/GNL knockout mice

作者：Takahashi Keita; Kishimoto Yuki; Konishi Tomokazu; Fujita Yasunori; Ito Masafumi; Shimokado Kentaro; Maruyama Naoki; Ishigami Akihito^*

来源：Biochimica et Biophysica Acta-General Subjects, 2014, 1840(7): 2289-2298.

DOI：10.1016/j.bbagen.2014.03.019

• Ascorbic acid
• Bile acid
• Cyp7a1
• Lipid metabolism
• Microarray
• Nrf2

Background: We 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. %26lt;br%26gt;Methods: We 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. %26lt;br%26gt;Results: Our microarray analysis revealed that the AA deficiency increased gene expression related to the oxidation-reduction process, i.e., the nuclear factor, elythroid 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 the cytochrome P450, family 7, subfamily a, polypeptide 1 (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. %26lt;br%26gt;Conclusions: This experimental evidence strongly supports a role for AA in the physiologic oxidation-reduction process and lipid metabolism including bile acid biosynthesis. %26lt;br%26gt;General significance: Although 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.

• 出版日期2014-7