Minc-Golomb D, Knobler H, Groner Y
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
EMBO J. 1991 Aug;10(8):2119-24. doi: 10.1002/j.1460-2075.1991.tb07745.x.
Patients with Down's syndrome (DS) exhibit elevated activity of copper zinc superoxide dismutase (CuZnSOD) caused by the trisomy 21 state. To investigate the possible involvement of CuZnSOD gene dosage in perturbation of prostaglandin biosynthesis we analyzed transfected cells and transgenic mice that express elevated levels of human CuZnSOD. It was found that the synthesis of prostaglandin E2 (PGE2) was diminished in transfected PC12-CuZnSOD cells as well as in fibroblasts from DS patients. Primary cells derived from transgenic CuZnSOD mice showed similar reduction. Impaired biosynthesis of prostaglandins was not confined to cells grown in culture since secretion of PGE2 and PGD2 by kidney and cerebellum of transgenic CuZnSOD was significantly lower than in non-transgenic littermate mice. These findings strongly suggest that overexpression of the CuZnSOD gene induces a demotion in PGE2 and PGD2 formation and establish a connection between alteration of prostaglandin biosynthesis in trisomy 21 cells and gene dosage of CuZnSOD.
唐氏综合征（DS）患者由于21号染色体三体状态，其铜锌超氧化物歧化酶（CuZnSOD）活性升高。为了研究CuZnSOD基因剂量可能参与前列腺素生物合成紊乱的情况，我们分析了表达高水平人CuZnSOD的转染细胞和转基因小鼠。结果发现，转染的PC12 - CuZnSOD细胞以及DS患者的成纤维细胞中前列腺素E2（PGE2）的合成减少。来自转基因CuZnSOD小鼠的原代细胞也表现出类似的减少。前列腺素生物合成受损并不局限于培养的细胞，因为转基因CuZnSOD小鼠的肾脏和小脑分泌的PGE2和PGD2明显低于非转基因同窝小鼠。这些发现强烈表明，CuZnSOD基因的过表达会导致PGE2和PGD2形成减少，并在21三体细胞中前列腺素生物合成的改变与CuZnSOD基因剂量之间建立联系。
