A functional analysis of a novel mitochondrial protein Apop-1 and its application to health sciences

我们以前已经确定了Apop-1基因，一种新的动脉粥样硬化特异性基因，编码一种线粒体蛋白。然而，其职能仍有待确定。我们发现，与野生型对照组相比，Apop-1-KO小鼠的葡萄糖耐量显著受损。在这些小鼠中，基线胰岛素和在GTT期间服用葡萄糖后的胰岛素水平显著较高。在MIN 6细胞中，高糖处理诱导Apop-1 mRNA表达显著降低。这些结果提示Apop-1可能参与了2型糖尿病的发生。在人脐静脉内皮细胞（HUVEC）中，我们认为Apop-1可能参与高糖诱导的线粒体ROS产生机制。此外，Apop-1基因多态性（rs 1288943）在年轻女性的遗传分析表明，在隐性模型中，血浆LPL活性显着降低T等位基因组与非T等位基因组相比。对年轻女性自填饮食史问卷（DHQ）估计的膳食纤维摄入量的评估显示，高摄入组的HOMA-IR和血浆TG水平显著低于低摄入组。然而，这种有益的作用，膳食纤维在T等位基因组消失。提示Apop-1基因多态性可能影响饮食习惯与胰岛素抵抗发生的关系。

We have previously identified the Apop-1 gene, a novel atherosclerosis-specific gene, which codes a mitochondrial protein. However, its functions remain to be determined. We showed that glucose tolerance was significantly impaired in Apop-1-KO mice compared with wild-type controls. Baseline insulin and insulin levels after taking glucose during the GTT were significantly higher in these mice. In MIN6 cells high glucose treatment induced a significant reduction of Apop-1 mRNA expression. These results suggest that Apop-1 might be involved in the genesis of type 2 diabetes mellitus. In human umbilical endothelial cells(HUVEC) we suggest that Apop-1 might be involved in the mechanism of mitochondrial ROS production induced by high glucose. Additionally, genetic analysis of Apop-1 gene polymorphism(rs1288943) in young women showed that in recessive model plasma LPL activity was significantly lower in T allele group compared with non-T allele group. Assessment of dietary fibers intake estimated from a self-administered diet history questionnaire(DHQ) in young women showed that levels of HOMA-IR and plasma TG were significantly lower in those with the higher intake group compared with the lower intake group. However, this beneficial effect of dietary fibers was disappeared in T allele group. These results suggest that Apop-1 gene polymorphism might affect the relation between dietary habit and the genesis of insulin resistance.