Glutathione depletion in antioxidant defense of differentiated NT2-LHON cybrids

被引：11

作者：

Schoeler, S.

Winkler-Stuck, K.

Szibor, R.

Haroon, M. F.

Gellerich, F. N.

Chamaon, K.

Mawrin, C.

Kirches, E. K.

机构：

[1] Dept Neuropathol, D-39120 Magdeburg, Germany

[2] Dept Neurol, D-39120 Magdeburg, Germany

[3] Dept Forens Med, D-39120 Magdeburg, Germany

[4] Otto Von Guericke Univ, Dept Med Neurobiol, D-39120 Magdeburg, Germany

[5] KeyNeurotek AG, D-39120 Magdeburg, Germany

来源：

NEUROBIOLOGY OF DISEASE | 2007年 / 25卷 / 03期

关键词：

LHON; antioxidant defense; glutathione; ROS; cybrid;

D O I：

10.1016/j.nbd.2006.10.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The mechanism of retinal ganglion cell loss in Leber's hereditary optic neuropathy (LHON) is still uncertain, and a role of enhanced superoxide production by the mutant mitochondrial complex I has been hypothesized. In the present study, it was shown that LHON cybrids, carrying the np11778 mutation, became selectively more H2O2 sensitive compared with the parental cell line only following short-term retinoic acid differentiation. They contained a decreased cellular glutathione pool (49%, p <= 0.05), despite 1.5-fold enhanced expression of the regulatory subunit of gamma-glutamylcysteine synthetase (p <= 0.05). This points to a reduction of the capacity to detoxify H2O2 and to changes in thiol redox potential. The activity of the H2O2 degrading enzyme glutathione peroxidase (GPx) and the activities of glutathione reductase (GR) and superoxide dismutase (SOD) were unaffected. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：536 / 544

页数：9

共 33 条

[11] Leber's hereditary optic neuropathy (LHON) pathogenic mutations induce mitochondrial-dependent apoptotic death in transmitochondrial cells incubated with galactose medium [J].