Extracellular-superoxide dismutase is a tetrameric copper-containing glycoprotein that previously has been demonstrated to be the major superoxide dismutase of human extracellular fluids. The occurrence of this enzyme in various human tissues that were removed from two accidental death victims and in 19 different human cultured cell lines was determined. All investigated tissues were found to c...

Pyrrolidine dithiocarbamate (PDTC) known as antioxidant and specific inhibitor of NF-κB was also described as pro-oxidant by inducing cell death and reactive oxygen species (ROS) accumulation in cancer. However, the mechanism by which PDTC indices its pro-oxidant effect is unknown. Therefore, we aimed to evaluate the effect of PDTC on the human Cu/Zn superoxide dismutase 1 (SOD1) gene transcrip...

The oxidative damage hypothesis proposed for the function gain of copper, zinc superoxide dismutase (SOD1) maintains that both mutant and wild-type (WT) SOD1 catalyze reactions with abnormal substrates that damage cellular components critical for viability of the affected cells. However, whether the oxidative damage of SOD1 is involved in the formation of aggregates rich in SOD1 or not remains ...

Diverse point mutations in the enzyme Cu, Zn superoxide dismutase (SOD1) are linked to its aggregation in the familial form of the disease amyotrophic lateral sclerosis. The disease-associated mutations are known to destabilize the protein, but the structural basis of the aggregation of the destabilized protein and the structure of aggregates are not well understood. Here, we investigate in sil...

Cu/Zn superoxide dismutase (SOD1) is an abundant enzyme that has been best studied as a regulator of antioxidant defense. Using the yeast Saccharomyces cerevisiae, we report that SOD1 transmits signals from oxygen and glucose to repress respiration. The mechanism involves SOD1-mediated stabilization of two casein kinase 1-gamma (CK1γ) homologs, Yck1p and Yck2p, required for respiratory repressi...

BACKGROUND AND PURPOSE Both NO and superoxide cytotoxicity are important in experimental stroke; however, it is unclear whether these molecules act within parallel pathological pathways or as coreagents in a common reaction. We examined these alternatives by comparing outcomes after middle cerebral artery occlusion in male and female neuronal NO synthase (nNOS)-deficient (nNOS-/-) or human CuZn...

We sought genetic evidence for the involvement of neuronal vascular endothelial growth factor (VEGF) in amyotrophic lateral sclerosis (ALS). Mice expressing human ALS mutant superoxide dismutase-1 (SOD1) were crossed with mice that overexpress VEGF in neurons (VEGF+/+). We report that SOD1(G93A)/VEGF+/+ double-transgenic mice show delayed motor neuron loss, delayed motor impairment, and prolong...

Motor axon degeneration is a critical but poorly understood event leading to weakness and muscle atrophy in motor neuron diseases. Here, we investigated oxidative stress-mediated axonal degeneration in mice lacking the antioxidant enzyme, Cu,Zn superoxide dismutase (SOD1). We demonstrate a progressive motor axonopathy in these mice and show that Sod1(-/-) primary motor neurons extend short axon...

Recently, a subgroup of the amyotrophic lateral sclerosis (ALS) syndrome associated with mutations in the gene encoding the free radical scavenging enzyme CuZn-superoxide dismutase (CuZn-SOD, SOD1) has been identified. Some 67 different mutations have been reported worldwide to date, comprising about one-fifth of familial ALS cases in the populations studied. The autosomal recessively inherited...