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The Glutathione System of Peroxide Detoxification Is Less Efficient in Neurons than in Astroglial Cells
Author(s) -
Dringen Ralf,
Kussmaul Lothar,
Gutterer Jan Mirko,
Hirrlinger Johannes,
Hamprecht Bernd
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722523.x
Subject(s) - cumene hydroperoxide , glutathione , incubation , catalase , biochemistry , chemistry , neuron , peroxidase , peroxide , glutathione peroxidase , antioxidant , hydrogen peroxide , biology , enzyme , neuroscience , organic chemistry , catalysis
The ability of neurons to detoxify exogenously appliedperoxides was analyzed using neuron‐rich primary cultures derived fromembryonic rat brain. Incubation of neurons with H 2 O 2 atan initial concentration of 100 μ M (300 nmol/3 ml) led to adecrease in the concentration of the peroxide, which depended strongly on theseeding density of the neurons. When 3 × 10 6 viable cellswere seeded per dish, the half‐time for the clearance by neurons ofH 2 O 2 from the incubation buffer was 15.1 min.Immediately after application of 100 μ M H 2 O 2 to neurons, glutathione was quickly oxidized. After incubation for 2.5 min,GSSG accounted for 48% of the total glutathione. Subsequent removal ofH 2 O 2 caused an almost complete regeneration of theoriginal ratio of GSH to GSSG within 2.5 min. Compared with confluentastroglial cultures, neuron‐rich cultures cleared H 2 O 2 more slowly from the incubation buffer. However, if the differences in proteincontent were taken into consideration, the ability of the cells to dispose ofH 2 O 2 was identical in the two culture types. Theclearance rate by neurons for H 2 O 2 was strongly reducedin the presence of the catalase inhibitor 3‐aminotriazol, a situationcontrasting with that in astroglial cultures. This indicates that for therapid clearance of H 2 O 2 by neurons, both glutathione peroxidase and catalase are essential and that the glutathione system cannot functionally compensate for the loss of the catalase reaction. In addition, the protein‐normalized ability of neuronal cultures to detoxify exogenous cumene hydroperoxide, an alkyl hydroperoxide that is reduced exclusively via the glutathione system, was lower than that of astroglial cells by a factor of 3. These results demonstrate that the glutathione system of peroxide detoxification in neurons is less efficient than that of astroglial cells.