Oncology Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
Biochem Biophys Res Commun. 2012 Jul 6;423(3):553-6. doi: 10.1016/j.bbrc.2012.06.002. Epub 2012 Jun 7.
D-2-hydroxyglutaric aciduria (D-2HGA) is a hereditary metabolic disorder characterized by the elevated levels of D-2-hydroxyglutaric acid (D-2HG) in urine, plasma and cerebrospinal fluid. About half of the patients have autosomal recessive mutations in D-2-hydroxyglutarate dehydrogenase (D2HGDH) gene. To analyze the origin of D-2HG in D2HGDH-depleted cells, we used small interfering RNA (siRNA) techniques. We found that knockdown of D2HGDH in MCF7 cells increased the levels of 2HG, mimicking D2HGDH mutant cells. Additional knockdown of isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) decreased the level of 2HG in D2HGDH knockdown MCF7 cells. Conversely, ectopic expression of IDH1 or IDH2 increased 2HG in MCF7 cells. These results suggest that IDH1 and IDH2 have roles in production of D-2HG in cells.
D-2-羟戊二酸尿症（D-2HGA）是一种遗传性代谢紊乱，其特征是尿液、血浆和脑脊液中 D-2-羟戊二酸（D-2HG）水平升高。约一半的患者存在 D-2-羟戊二酸脱氢酶（D2HGDH）基因的常染色体隐性突变。为了分析 D2HGDH 耗尽细胞中 D-2HG 的来源，我们使用了小干扰 RNA（siRNA）技术。我们发现，MCF7 细胞中 D2HGDH 的敲低增加了 2HG 的水平，模拟了 D2HGDH 突变细胞。IDH1 或 IDH2 的额外敲低降低了 D2HGDH 敲低 MCF7 细胞中的 2HG 水平。相反，IDH1 或 IDH2 的异位表达增加了 MCF7 细胞中的 2HG。这些结果表明 IDH1 和 IDH2 在细胞中 D-2HG 的产生中起作用。
