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The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme

The Cu,Zn superoxide dismutase (SOD1) is an ubiquitary cytosolic dimeric carbohydrate free molecule, belonging to a family of isoenzymes involved in the scavenger of superoxide anions. This effect certainly represents the main and well known function ascribed to this enzyme. Here we highlight new as...

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Autores principales: Mondola, Paolo, Damiano, Simona, Sasso, Anna, Santillo, Mariarosaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126113/
https://www.ncbi.nlm.nih.gov/pubmed/27965593
http://dx.doi.org/10.3389/fphys.2016.00594
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author Mondola, Paolo
Damiano, Simona
Sasso, Anna
Santillo, Mariarosaria
author_facet Mondola, Paolo
Damiano, Simona
Sasso, Anna
Santillo, Mariarosaria
author_sort Mondola, Paolo
collection PubMed
description The Cu,Zn superoxide dismutase (SOD1) is an ubiquitary cytosolic dimeric carbohydrate free molecule, belonging to a family of isoenzymes involved in the scavenger of superoxide anions. This effect certainly represents the main and well known function ascribed to this enzyme. Here we highlight new aspects of SOD1 physiology that point out some inedited effects of this enzyme in addition to the canonic role of oxygen radical enzymatic dismutation. In the last two decades our research group produced many data obtained in in vitro studies performed in many cellular lines, mainly neuroblastoma SK-N-BE cells, indicating that this enzyme is secreted either constitutively or after depolarization induced by high extracellular K(+) concentration. In addition, we gave many experimental evidences showing that SOD1 is able to stimulate, through muscarinic M1 receptor, pathways involving ERK1/2, and AKT activation. These effects are accompanied with an intracellular calcium increase. In the last part of this review we describe researches that link deficient extracellular secretion of mutant SOD1(G93A) to its intracellular accumulation and toxicity in NSC-34 cells. Alternatively, SOD1(G93A) toxicity has been attributed to a decrease of K(m) for H(2)O(2) with consequent OH radical formation. Interestingly, this last inedited effect of SOD1(G93A) could represent a gain of function that could be involved in the pathogenesis of familial Amyotrophic Lateral Sclerosis (fALS).
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spelling pubmed-51261132016-12-13 The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme Mondola, Paolo Damiano, Simona Sasso, Anna Santillo, Mariarosaria Front Physiol Physiology The Cu,Zn superoxide dismutase (SOD1) is an ubiquitary cytosolic dimeric carbohydrate free molecule, belonging to a family of isoenzymes involved in the scavenger of superoxide anions. This effect certainly represents the main and well known function ascribed to this enzyme. Here we highlight new aspects of SOD1 physiology that point out some inedited effects of this enzyme in addition to the canonic role of oxygen radical enzymatic dismutation. In the last two decades our research group produced many data obtained in in vitro studies performed in many cellular lines, mainly neuroblastoma SK-N-BE cells, indicating that this enzyme is secreted either constitutively or after depolarization induced by high extracellular K(+) concentration. In addition, we gave many experimental evidences showing that SOD1 is able to stimulate, through muscarinic M1 receptor, pathways involving ERK1/2, and AKT activation. These effects are accompanied with an intracellular calcium increase. In the last part of this review we describe researches that link deficient extracellular secretion of mutant SOD1(G93A) to its intracellular accumulation and toxicity in NSC-34 cells. Alternatively, SOD1(G93A) toxicity has been attributed to a decrease of K(m) for H(2)O(2) with consequent OH radical formation. Interestingly, this last inedited effect of SOD1(G93A) could represent a gain of function that could be involved in the pathogenesis of familial Amyotrophic Lateral Sclerosis (fALS). Frontiers Media S.A. 2016-11-29 /pmc/articles/PMC5126113/ /pubmed/27965593 http://dx.doi.org/10.3389/fphys.2016.00594 Text en Copyright © 2016 Mondola, Damiano, Sasso and Santillo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Mondola, Paolo
Damiano, Simona
Sasso, Anna
Santillo, Mariarosaria
The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme
title The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme
title_full The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme
title_fullStr The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme
title_full_unstemmed The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme
title_short The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme
title_sort cu, zn superoxide dismutase: not only a dismutase enzyme
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126113/
https://www.ncbi.nlm.nih.gov/pubmed/27965593
http://dx.doi.org/10.3389/fphys.2016.00594
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