Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis is a fatal paralytic disorder of unknown cause. Recent evidence implicated the role of free radicals in the death of motor neurons in this disease. To investigate this hypothesis further, we measured the activity of the main free radical scavenging enzymes copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in postmortem brain samples from 9 patients with sporadic amyotrophic lateral sclerosis and from 9 control subjects. We examined samples from the precentral gyrus of the cerebral cortex, a region affected in amyotrophic lateral sclerosis, and from the cerebellar cortex, a region not affected. The two groups did not differ in age or postmortem delay. In the precentral gyrus from amyotrophic lateral sclerosis samples, glutathione peroxidase activity as measured by spectrophotometric assay (13.8 +/- 2.6 nmol/min/mg protein [mean +/- standard error of mean]) was reduced significantly compared to the activity in the precentral gyrus from control samples (22.7 +/- 0.5 nmol/min/mg protein). In contrast, glutathione peroxidase activity was not significantly altered in the cerebellar cortex from amyotrophic lateral sclerosis patients compared to controls. Copper/zinc superoxide dismutase, manganese superoxide dismutase (corrected or not corrected for citrate synthase), and catalase were not significantly altered in the precentral gyrus or cerebellar cortex in the patient samples. This study indicated that glutathione peroxidase activity is reduced in a brain region affected in amyotrophic lateral sclerosis, thus suggesting that free radicals may be implicated in the pathogenesis of the disease.

Oxidant treatment causes a dose-dependent phenotype of apoptosis in cultured motoneurons

“…In this study, we have shown that ROS-induced motoneuron death can be blocked with catalase, the enzyme that converts hydrogen peroxide into water. Although recent studies revealed no decreased catalase levels in ALS patients (Przedborski et al, 1996), it is very well possible that extra catalase, delivered by intrathecally implanted polymer encapsulated cells (Sagot et al, 1995), could be beneficial for ALS patients.…”

Decrease in Asymmetrical Dimethylarginine, an Endogenous Nitric Oxide Synthase Inhibitor, in Cerebrospinal Fluid during Elderly Aging and in Patients with Sporadic Form of Amyotrophic Lateral Sclerosis

“…Regarding reactive oxygen species and ALS, there are numerous supportive previous studies lending support to the contribution of reactive oxygen species to ALS. A pathological study showed that glutathione peroxidase activity deteriorated in the precentral cortex in autopsies of ALS afflicted cerebrum [21] . Immunohistochemical studies have demonstrated the upregulated stainability of 8-hydroxy-2-deoxyguanosine, a DNA nucleic acid injury marker of brain during autopsy of the ALS motor cortex and spinal cord [22] .…”

Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis

“…At autopsy, brains and spinal cords were removed and processed for banking as previously described. 26 Half of the brain and blocks from various levels of the spinal cord were placed in 10% buffered formalin and were subjected to neuropathological examination. The other half of the brain and the rest of the spinal cord blocks were immediately frozen on dry ice and stored at Ϫ80°C until used.…”