Molecular Basis of Familial Glucocorticoid Deficiency

本项目的目标是：1)验证NNT缺陷在体外和体内损害细胞氧化还原状态和线粒体生物能量学；2)验证受损的细胞氧化还原状态介导MAPK通路抑制线粒体三磷酸腺苷的产生，诱导细胞凋亡并随后降低细胞存活率；3)寻找与FGD相关的新基因并阐明其潜在的机制(S)。NNT基因敲除导致HAC15细胞(人肾上腺皮质细胞系)氧化还原状态和线粒体生物能量学受损。2.NNT缺乏的FGD患者淋巴细胞线粒体ROS生成率较高，提示NNT缺乏导致患者氧化应激增加。由于缺乏血液样本，没有进行NNT缺乏对FGD患者线粒体生物能量学的影响，由于研究人员退休，所有剩余的实验都停止了。

The objectives of this project are 1) to verify NNT defect impairs cellular redox status and mitochondrial bioenergetics both in vitro and in vivo; 2) to validate the impaired cellular redox status mediates MAPK pathways to inhibit mitochondrial ATP production and induce apoptosis and subsequent decreased cellular viability; 3) to identify new genes responsible for FGD and elucidate the underlying mechanism(s)The following results were obtained.1. NNT knockdown resulted in an oxidized cellular redox status and impaired mitochondrial bioenergetics in HAC15 cells (a human adrenocortical cell line)2. The FGD patient with NNT deficiency showed higher ROS production rate in the lymphocytic mitochondria, suggesting NNT deficiency lead to increased oxidative stress in the patient.3. The effect of NNT deficiency on mitochondrial bioenergetics in the FGD patient was not performed due to lack of blood sample and all the remaining experiments were stopped due to the researcher’s retirement.