Role of vitamin A in mitochondrial gene expression
Role of vitamin A in mitochondrial gene expression
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DOI：
10.1016/s0168-8227(01)00331-x
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发表时间：
2001-12-01
影响因子：
5.1
通讯作者：
Mathews, CE
中科院分区：
文献类型：
--
作者：
Berdanier, CD;Everts, HB;Mathews, CE
研究了糖尿病易感BHE/Cdb和SD大鼠线粒体（mt）功能和mt基因表达。BHE/Cdb大鼠携带线粒体ATP酶6基因突变，表现为OXPHOS效率降低，随后出现糖耐量受损。碱基取代导致质子通道中的氨基酸取代，这反过来。影响ATP分子的能量捕获效率。喂养研究表明，BHE/Cdb大鼠需要10倍以上的维生素E和3倍以上的维生素A在他们的饮食比正常的SD大鼠。维生素A补充“正常化”mt OXPHOS以及增加mt隔室中ATP酶亚基a蛋白的量。维甲酸受体在线粒体和核室的蛋白质印迹分析表明，这些蛋白质都存在于mt室。补充维生素A的效果加上对维甲酸受体的观察表明，维生素A具有增强ATP酶6基因转录的功能。使用肝细胞的原代培养物。表明，不仅视黄酸增加线粒体ATP酶6基因的表达，而且类固醇激素中间体脱氢表雄酮（DHEA）也是如此。三碘甲状腺原氨酸也在这一过程中发挥作用，但不是一个独立的因素。相反，这种激素增强视黄酸和DHEA对ATP酶基因表达的影响。这些结果表明，mt基因的表达需要的不仅仅是mt转录因子A。更有可能的是，这个过程需要许多因素，就像核基因表达一样。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Diabetes-prone BHE/Cdb and Sprague-Dawley (SD) rats were studied with respect to mitochondrial (mt) function and mt gene expression. The BHE/Cdb rats carry mutations in the mt ATPase 6 gene that phenotype as decreased OXPHOS efficiency with subsequent development of impaired glucose tolerance. The base substitutions result in amino acid substitutions in the proton channel and this, in turn. affects the efficiency of energy capture in the ATP molecule. Feeding Studies showed that BHE/Cdb rats required 10 times more vitamin E and three times more vitamin A in their diets than do normal SD rats. Vitamin A supplementation 'normalized' mt OXPHOS as well as increased the amount of ATPase subunit a protein in the mt compartment. Western blot analysis of retinoic acid receptors in the mitochondrial and nuclear compartments showed that these proteins were present in the mt compartment. The effect of the vitamin A supplementation plus the observation of retinoic acid receptors suggest that vitamin A functions to enhance the transcription of the ATPase 6 gene. Work with primary cultures of hepatocytes. showed that not only does retinoic acid increase mitochondrial ATPase 6 gene expression but so too does the steroid hormone intermediate, dehydroepiandrosterone (DHEA). Triiodothyronine also plays a role in this process but not as an independent factor. Rather, this hormone potentiates the effects of retinoic acid and DHEA on ATPase gene expression. These results suggest that mt gene expression requires more than just the mt transcription factor A. More than likely the process requires a number of factors in much the same way as does nuclear gene expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.