A new perspective on the role of CuZn superoxide dismutase (SOD1)

AbstractThe CuZn superoxide dismutase (SOD1), a member of a group of isoenzymes involved in the scavenger of superoxide anions, is a dimeric carbohydrate free protein, mainly localized in the cytosol. The reactive oxygen species (ROS) are involved in many pathophysiological events correlated with mutagenesis, cancer, degenerative processes and aging. In the first part of this mini-review the well known role of SOD1 and ROS are briefly summarized. Following, a potential novel biological action that SOD1 could exert is described, based on the recent researches demonstrating the secretion of this enzyme in many cellular lines. Moreover, the role of impaired mutant SOD1 secretion, associated with cytoplasmic toxic inclusion, which occurs in familial amyotrophic lateral sclerosis (ALS), is summarized. In addition, a depolarization-dependent release of SOD1 in pituitary GH3 cells and in rat synaptosomes through a calcium and SNARE-dependent mechanism is reported.

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Superoxide Dismutase 2 Deficient Mice: The Role of Increased Reactive Oxygen Species in Genomic Instability

Oxidative Stress, Disease and Cancer ◽

10.1142/9781860948046_0011 ◽

2006 ◽

pp. 357-369

Author(s):

Enrique Samper ◽

Chris Benz ◽

Simon Melov

Keyword(s):

Reactive Oxygen Species ◽

Superoxide Dismutase ◽

Genomic Instability ◽

Reactive Oxygen ◽

Oxygen Species ◽

Deficient Mice ◽

Superoxide Dismutase 2

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Role of superoxide dismutase in the pathogenesis of amyotrophic lateral sclerosis

Bulletin of Experimental Biology and Medicine ◽

10.1007/bf02433397 ◽

1999 ◽

Vol 127 (4) ◽

pp. 417-419 ◽

Cited By ~ 1

Author(s):

M. N. Zakharova ◽

I. A. Zavalishin ◽

A. A. Boldyrev ◽

O. S. Brusov ◽

O. A. Pavlova

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Superoxide Dismutase ◽

Lateral Sclerosis

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Oxidation of the Tryptophan 32 Residue of Human Superoxide Dismutase 1 Caused by Its Bicarbonate-dependent Peroxidase Activity Triggers the Non-amyloid Aggregation of the Enzyme

Journal of Biological Chemistry ◽

10.1074/jbc.m114.586370 ◽

2014 ◽

Vol 289 (44) ◽

pp. 30690-30701 ◽

Cited By ~ 23

Author(s):

Fernando R. Coelho ◽

Asif Iqbal ◽

Edlaine Linares ◽

Daniel F. Silva ◽

Filipe S. Lima ◽

...

Keyword(s):

Superoxide Dismutase ◽

Peroxidase Activity ◽

Oxidation Products ◽

Superoxide Dismutase 1 ◽

Amyloid Aggregation ◽

Post Translational Modifications ◽

Covalent Dimer ◽

Als Patients ◽

Lateral Sclerosis

The role of oxidative post-translational modifications of human superoxide dismutase 1 (hSOD1) in the amyotrophic lateral sclerosis (ALS) pathology is an attractive hypothesis to explore based on several lines of evidence. Among them, the remarkable stability of hSOD1WT and several of its ALS-associated mutants suggests that hSOD1 oxidation may precede its conversion to the unfolded and aggregated forms found in ALS patients. The bicarbonate-dependent peroxidase activity of hSOD1 causes oxidation of its own solvent-exposed Trp32 residue. The resulting products are apparently different from those produced in the absence of bicarbonate and are most likely specific for simian SOD1s, which contain the Trp32 residue. The aims of this work were to examine whether the bicarbonate-dependent peroxidase activity of hSOD1 (hSOD1WT and hSOD1G93A mutant) triggers aggregation of the enzyme and to comprehend the role of the Trp32 residue in the process. The results showed that Trp32 residues of both enzymes are oxidized to a similar extent to hSOD1-derived tryptophanyl radicals. These radicals decayed to hSOD1-N-formylkynurenine and hSOD1-kynurenine or to a hSOD1 covalent dimer cross-linked by a ditryptophan bond, causing hSOD1 unfolding, oligomerization, and non-amyloid aggregation. The latter process was inhibited by tempol, which recombines with the hSOD1-derived tryptophanyl radical, and did not occur in the absence of bicarbonate or with enzymes that lack the Trp32 residue (bovine SOD1 and hSOD1W32F mutant). The results support a role for the oxidation products of the hSOD1-Trp32 residue, particularly the covalent dimer, in triggering the non-amyloid aggregation of hSOD1.

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