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Calcineurin activity is regulated both by redox compounds and by mutant familial amyotrophic lateral sclerosis-superoxide dismutase

TitleCalcineurin activity is regulated both by redox compounds and by mutant familial amyotrophic lateral sclerosis-superoxide dismutase
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2000
AuthorsFerri, A., Gabbianelli R., Casciati Arianna, Paolucci E., Rotilio G., and Carrì M.T.
JournalJournal of Neurochemistry
Volume75
Pagination606-613
ISSN00223042
Keywordsamyotrophic lateral sclerosis, Animals, article, Ascorbic acid, calcineurin, Calcium, calcium transport, Cultured, Dithiothreitol, enzyme activity, hippocampus, human, human cell, Humans, Mice, Motor Cortex, Motor Neuron Disease, Mus musculus, Neuroblastoma, oxidation reduction reaction, Oxidation-Reduction, Oxidative stress, pathogenesis, priority journal, Recombinant Proteins, Spinal Cord, superoxide dismutase, Transfection, Transgenic, Tumor Cells
Abstract

Calcineurin (CN) is a protein phosphatase involved in a wide range of cellular responses to calcium-mobilizing signals, and a role for this enzyme in neuropathology has been postulated. We have investigated the possibility that redox modulation of CN activity is relevant to neuropathological conditions where an imbalance in reactive oxygen species has been described. We have monitored CN activity in cultured human neuroblastoma SH-SY5Y cells and obtained evidence that CN activity is promoted by treatment with ascorbate or dithiothreitol and impaired by oxidative stress. Evidence for the existence of a redox regulation of this enzyme has been also obtained by overexpression of wild-type antioxidant Cu,Zn superoxide dismutase (SOD1) that promotes CN activity and protects it from oxidative inactivation. On the contrary, overexpression of mutant SOD1s associated with familial amyotrophic lateral sclerosis (FALS) impairs CN activity both in transfected human neuroblastoma cell lines and in the motor cortex of brain from FALS- transgenic mice. These data suggest that CN might be a target in the pathogenesis of SOD1-linked FALS.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-0033914937&doi=10.1046%2fj.1471-4159.2000.0750606.x&partnerID=40&md5=fac70e8be631412ac0505ca101a1076a
DOI10.1046/j.1471-4159.2000.0750606.x
Citation KeyFerri2000606