Enhanced neuronal protection from oxidative stress by coculture with glutamic acid decarboxylase-expressing astrocytes

被引:35
作者
Lamigeon, C
Bellier, JP
Sacchettoni, S
Rujano, M
Jacquemont, B
机构
[1] RTH Laennec, Fac Med, Lab Neuro Virol Mol, Lyon, France
[2] RTH Laennec, Fac Med, Lab Neurobiol Expt & Physiopathol, Lyon, France
[3] Sch Med JM Vargas, Neurosurg & Physiol Dept, Caracas, Venezuela
关键词
GAD67; transgene; glutathione; neuroprotection; PC12;
D O I
10.1046/j.1471-4159.2001.00278.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Astrocytes expressing glutamic acid decarboxylase GAD67 directed by the glial fibrillary acidic protein promoter were shown to provide enhanced protection of PC12 cells from H2O2 treatment and serum deprivation in the presence of glutamate. In addition, they protected non-differentiated, but not differentiated, embryonic rat cortical neurons from glutamate toxicity. Glutamic acid decarboxylase (GAD)expressing astrocytes showed increased glutathione synthesis and release compared to control astrocytes. These changes were due to GAD transgene expression, as transient expression of a GAD antisense plasmid resulted in partial suppression of the increase in glutathione release. In addition to the previously demonstrated increases in NADH and ATP levels and lactate release, GAD-expressing astrocytes show increased antioxidant activity, explaining their ability to protect neurons from various injuries.
引用
收藏
页码:598 / 606
页数:9
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