Increase In Manganese Superoxide Dismutase Research Articles

High levels of Mn-superoxide dismutase in serum of patients with neuroblastoma and in human neuroblastoma cell lines

Levels of serum manganese superoxide dismutase (Mn-SOD) in normal children aged from 1 to 14 years and children with various hematological and malignant diseases were determined by enzyme-linked immunosorbent assay (ELISA). In the normal children, the serum Mn-SOD levels gradually increased in proportion to age. By 8 years of age, the Mn-SOD level was nearly at the adult level. The normal values of serum Mn-SOD (mean ± SD) of children below 4 and above 8 years old were 48 ± 10.2 ng/ml and 84 ± 22.5 ng/ml, respectively. Assuming the upper limit of normal Mn-SOD level in serum to be the mean value ± 2 SD of children at each age, high serum levels of Mn-SOD were found for 8 of 12 patients with neuroblastoma, three of four patients with Wilms tumor, and four of five patients with acute myeloid leukemia. The patients with neuroblastoma exhibited a transient increase in Mn-SOD following chemotherapy, but after 1 week the levels decreased markedly to the control levels. The changes in serum Mn-SOD levels in the patients with neuroblastoma correlated well with the levels of neuron-specific enolase. Mn-SOD was intensely stained in bone marrow cells of patients whose cancer cells had moved into the bone marrow. High levels of Mn-SOD were also found in cultured human neuroblastoma cells. These data indicate that Mn-SOD is expressed in neuroblastoma cells, may serve as one of the diagnostic and prognostic markers for the neuroblastoma, and may be useful to predict the effectiveness of chemotherapy for neuroblastoma and the recurrence of this disease.

Anaerobic biosynthesis of the manganese-containing superoxide dismutase in Escherichia coli.

Iron, particularly in the ferrous state plays a role in regulating the biosynthesis of the manganese superoxide dismutase (MnSOD) in Escherichia coli B. Addition of iron has a repressive effect on the synthesis of MnSOD under normal or inducing conditions (i.e. in the presence of paraquat). Addition of manganese to cultures already depressed for MnSOD biosynthesis causes a further increase in the amount of active enzyme, however, this effect is also abolished by the addition of iron. Removal of metals from the growth medium by Chelex 100 also derepresses the synthesis of MnSOD but repletion of the medium with iron abolishes this effect. Chelators specific for Fe2+, 2,2'-dipyridyl, and 1,10-phenanthroline, cause a 5-7-fold increase in MnSOD. Removal of iron also increases the synthesis of MnSOD in the absence of oxygen. A model is presented to account for the observed effects of oxygen, superoxide anion, and chelators on the increased synthesis of MnSOD. In this model, the regulatory repressor for MnSOD biosynthesis is envisioned as being an iron-containing protein.

Superoxide dismutase levels following liver and kidney intoxication.

The behavior of superoxide dismutase (SOD) in inflammatory lesions is interesting, because SOD is a scavenger of superoxide anion radical which is produced to excess in inflammation. In order to clarify the relationship between diseases and SOD levels in serum, we induced renal damage in the rabbit or liver damage in the rabbit and guinea pig, and then monitored the SOD levels and other clinical values. We observed the increase of serum cuprozinc-superoxide dismutase (Cu, Zn-SOD) concentration following kidney intoxication caused by the ligation of renal artery, and the increase of manganese-superoxide dismutase (Mn-SOD) concentration following liver intoxication caused by the injection of carbon tetrachloride. From these results, we confirmed the reports that serum Cu, Zn-SOD and Mn-SOD concentrations were markedly increased in patients with renal diseases and liver diseases, respectively.