The pathology of
Parkinson's disease involves oxidative damage to dopaminergic neurons of the substantia nigra. Oxidation of the
dopamine (DA)
neurotransmitter itself may contribute to the generation of a
reactive oxygen species (ROS) and subsequent neurodegeneration. Glia cells can either exacerbate injury or exert protective properties on local neurons in the brain. We investigate glial
antioxidant enzyme systems relative to ROS generated during
cytokine activation,
monoamine oxidase (
MAO) activity and autoxidation of DA in
glioma cells. Rat C6
glioma cells stimulated with
lipopolysaccharide Escherichia coli 0111:B4 and
interferon gamma (LPS/IFN-g) produced high levels of
nitric oxide (241 nmol mg(-1)
protein 24 h(-1)) but not
superoxide (O(-) (2)) or
hydrogen peroxide (H(2)O(2)). Basal C6 cells exhibited a rapid and robust capacity to remove exogenous H(2)O(2) within minutes. Preincubation with
sodium azide but not
buthionine-[S, R]-sulfoximine attenuated this response, indicating
catalase as the primary
enzyme responsible for this effect. The
glioma catalase reaction rate was slightly attenuated by exposure to LPS/IFN-g for 24 h. However, the reduction in
catalase activity was not due to
nitric oxide, because both the supernatant and
sodium nitroprusside had no effect on isolated
catalase enzyme activity.
Hydrogen peroxide was produced only through substrate-driven
MAO activity in prepared lysate. However, the quantity of H(2)O(2) produced per unit time (0.46 nmol mg(-1)
protein min(-1)) was negligible compared with the enormous capacity for its removal by
catalase (213.9 nmol mg(-1)
protein min(-1)) (>
or =462 x greater). Similarly, H(2)O(2) generated by DA autoxidation per unit time (0.28 nmol mg(-1)
protein equiv. min(-1)), was rapidly dissolved by
glioma cells at high capacity (> or =750 x greater). In conclusion, C6 cells produce
nitric oxide under
cytokine/
endotoxin-stimulated conditions. Moreover, C6 cells exhibit a dynamic H(2)O(2) scavenging capacity, with ample facility to dispose of the
peroxide generated by both
MAO activity and spontaneous DA autoxidation.