Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients to oxidative stress

Annals of Neurology
T AguirreW Robberecht

Abstract

Although the cause of amyotrophic lateral sclerosis (ALS) is unkNown, free radical toxicity is thought to play a pathogenic role. We investigated whether cells from ALS patients are more vulnerable to exogenously induced oxidative stress than cells from controls. We therefore studied the sensitivity of fibroblasts from patients with sporadic ALS (SALS), and from patients with familial ALS (FALS) associated with copper/zinc superoxide dismutase (Cu/ZnSOD) mutations (SOD1-FALS), to the free radical-generating agents 3-morpholinosydnonimine (SIN-1) and hydrogen peroxide (H2O2), and to serum withdrawal. SOD1-FALS and SALS fibroblasts were significantly more sensitive than controls to SIN-1 but not to serum withdrawal. In addition, SOD1-FALS fibroblasts were more sensitive to H2O2 than SALS fibroblasts and than fibroblasts of controls. These results suggest that the mechanism underlying both SOD1-FALS and SALS jeopardizes the cell's defense against free radical stress, and that SOD1-FALS cells are particularly sensitive to H2O2. The latter finding is compatible with biochemical data on the increased affinity of the mutated Cu/ZnSOD for H2O2.

References

Jan 1, 1987·CRC Critical Reviews in Biochemistry·J V BannisterG Rotilio
Oct 1, 1994·Neurochemistry International·K WellsL A Horrocks
Oct 1, 1995·Annals of Neurology·P J ShawD Mantle
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·S RabizadehD E Bredesen
Aug 12, 1993·Nature·J S BeckmanW H Koppenol

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Citations

Jul 2, 2003·Neurotoxicity Research·M B YimE R Stadtman
Jun 5, 2003·Pharmacology & Therapeutics·Michael J Strong
Apr 24, 1999·BMJ : British Medical Journal·P J Shaw
Jul 19, 2005·Journal of Neurology, Neurosurgery, and Psychiatry·P J Shaw
Feb 5, 2009·Orphanet Journal of Rare Diseases·Lokesh C Wijesekera, P Nigel Leigh
May 1, 2012·Journal of Molecular Biology·Vikram Khipple MulliganAvijit Chakrabartty
Sep 9, 2011·Journal of the American Academy of Nurse Practitioners·Melanie Davis, Jau-Shin Lou
Jun 19, 2004·Free Radical Biology & Medicine·Hanae NakashimaShigetoshi Kuroda
Jun 26, 2013·Free Radical Biology & Medicine·Emanuele D'AmicoHiroshi Mitsumoto
May 7, 2016·Acta Neuropathologica Communications·Elisa OnestoAntonia Ratti
Mar 23, 2004·Journal of Cellular Biochemistry·Bradley J TurnerSurindar S Cheema
Jul 30, 2019·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Gessica SalaLucio Tremolizzo
Apr 27, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·W A PedersenM P Mattson
Dec 14, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D LiuL Li
Dec 15, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jarosław WalczakJoanna Szczepanowska
Feb 16, 1999·Brain Pathology·M R Cookson, P J Shaw

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