The Effects of Human Wild-Type and Fals Mutant L144P SOD1 on Non-Vascular Smooth Muscle Contractions / EFEKTI HUMANE NORMALNE I FALS MUTIRANE L144P SOD1 NA NEVASKULARNE KONTRAKCIJE GLATKIH MIŠIĆA

Abstract

Summary Background: Mutated copper, zinc-containing superoxide dismutase (SOD1) may self-aggregate, an event that could also be an initial cause of motor neuron malfunction leading to disease onset. The effects of human mutated SOD1 pro- tein from the blood of familial amyotrophic lateral sclerosis (FALS) patients bearing Leu144Phe (L144F) mutation were compared to wild-type (WT) human SOD1 derived from healthy examinees, for enzymatic activity and the effects on isometric contractions of non-vascular smooth muscle. Methods: We isolated WT and L144F SOD1 enzymes from eight patients with FALS, L144F mutation in exon 5 and eight healthy controls. We then investigated SOD1 activities in the obtained samples by the adrenaline method and pro- filed them electrophoretically. Finally, we applied WT and L144F SOD1 on the isolated rat uterus. Results: L144F SOD1 showed lower superoxide-dismutating activity compared to WT human SOD1. We found that, in contrast to WT human SOD1, mutated L144F does not induce smooth muscle relaxation. Conclusions: Our data suggest that the lack of relaxation of muscle tonus in the presence of mutated SOD1 may have pathogenic feedback effects in FALS.