Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Precursor human manganese-dependent superoxide dismutase (hMn-SOD) was expressed using the baculovirus system in Spodoptera fungiperda (Sf-9) insect cells. Following infection of Sf-9 cells with hMn-SOD-expressing baculovirus, mature hMn-SOD was expressed at 15-25% of total cellular protein, with the recombinant protein localized in the mitochondrial matrix. Partial amino acid sequencing and SOD activity assays indicated that the hMn-SOD was correctly processed and assembled by insect mitochondria. This expression system was used to study the effects of paraquat and menadione, two intracellular superoxide generators, on processing of precursor hMn-SOD by insect mitochondria. Paraquat was found to potently inhibit mitochondrial processing of hMn-SOD, leading to the accumulation of precursor hMn-SOD and a decrease in measurable Mn-SOD activity. In contrast, menadione treatment was not found to affect the ratio of precursor to mature Mn-SOD. Paraquat did not lead to lower total production of hMn-SOD or cellular toxicity at the concentrations which were found to block processing of precursor hMn-SOD. These results indicate that mitochondrial processing and import of the precursor protein hMn-SOD are early events susceptible to dysfunction induced by the redox-cycling agent paraquat. These results also emphasize that mitochondrial processing of precursor proteins represents a parameter of cellular function which may be compromised, preceding the appearance of more generalized deterioration of cellular function, under certain toxic or pathological conditions.
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PMID:Paraquat inhibits the processing of human manganese-dependent superoxide dismutase by SF-9 insect cell mitochondria. 922 72

We report Mn superoxide dismutase (SOD) protein and activity in a patient with familial autosomal recessive Lewy body-negative parkinsonism in comparison with patients with sporadic Parkinson's disease (PD) and controls. We recently proved linkage of this family with markers of chromosome 6 at 6q25.2-27, which included the Mn SOD gene. We used a novel polymorphic mutation at -9 position of the signal peptide of the Mn SOD precursor protein, which caused valine to alanine substitution. All the affected members of this family showed homozygosity for alanine, whereas nonaffected members, sporadic PD patients, and the control subjects studied showed either heterozygosity of alanine and valine or homozygosity of valine. The Mn SOD activity of this familial patient was the highest among the PD patients and the control subjects studied, and an abundant expression of Mn SOD was found in the substantia nigra. The molecular weight of Mn SOD protein by Western blotting of this patient was essentially similar to that of PD patients and the control subjects. High Mn SOD activity may constitute a genetic risk factor in this familial patient. The difference in the signal peptide sequence may affect the expression of Mn SOD within mitochondria; however, it is unlikely that loss of function type Mn SOD mutation is the cause of this familial parkinsonism. Mn SOD in sporadic PD patients was similar to that in controls.
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PMID:Mn SOD activity and protein in a patient with chromosome 6-linked autosomal recessive parkinsonism in comparison with Parkinson's disease and control. 937 4