Abstract
In this work we compared the mutated liver copper zinc-containing superoxide dismutase (SOD1) protein G93A of the transgenic rat model of familial amyotrophic lateral sclerosis (FALS), to wild-type (WT) rat SOD1. We examined their enzymatic activities and effects on isometric contractions of uteri of healthy virgin rats. G93A SOD1 showed a slightly higher activity than WT SOD1 and, in contrast to WT SOD1, G93A SOD1 did not induce smooth muscle relaxation. This result indicates that effects on smooth muscles are not related to SOD1 enzyme activity and suggest that heterodimers of G93A SOD1 form an ion-conducting pore that diminishes the relaxatory effects of SOD1. We propose that this type of pathogenic feedback affects neurons in FALS.
Highlights
About 2% of amyotrophic lateral sclerosis (ALS) cases are familial (FALS), and have been associated with more than 150 different mutations on the SOD1 gene (Kiernan et al, 2011)
Some SOD1 mutations do not result in decreased SOD1 activity, they are observed in familial amyotrophic lateral sclerosis (FALS) (Goto et al, 2000; Siddique and Siddique, 2008)
The results presented here show that, in contrast to WT SOD1, G93A SOD1 does not induce smooth muscle relaxation
Summary
About 2% of amyotrophic lateral sclerosis (ALS) cases are familial (FALS), and have been associated with more than 150 different mutations on the SOD1 gene (Kiernan et al, 2011). SOD1 represents a soluble cytoplasmic and mitochondrial intermembrane space protein, whose function is to convert the superoxide radical anion (O2-) to hydrogen peroxide (H2O2) (Fridovich, 1989). Some SOD1 mutations do not result in decreased SOD1 activity, they are observed in FALS (Goto et al, 2000; Siddique and Siddique, 2008). This implies that the protein structure could play an important role independently of enzyme function. Mutated SOD proteins may self-aggregate, which represents an event that could be an initial cause of motor neuron malfunction leading to disease onset (Durham et al, 2007). The effects can be extracellular, since SOD1 is known to be excreted from the neurons
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