Increased SOD1 association with chromatin, DNA damage, p53 activation, and apoptosis in a cellular model of SOD1-linked ALS

Biochimica Et Biophysica Acta
Livea F BarbosaMarisa H G Medeiros

Abstract

Mutations in the gene encoding cytosolic Cu,Zn-superoxide dismutase (SOD1) have been linked to familial amyotrophic lateral sclerosis (FALS). However the molecular mechanisms of motor neuron death are multi-factorial and remain unclear. Here we examined DNA damage, p53 activity and apoptosis in SH-SY5Y human neuroblastoma cells transfected to achieve low-level expression of either wild-type or mutant Gly(93)-->Ala (G93A) SOD1, typical of FALS. DNA damage was investigated by evaluating the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and DNA strand breaks. Significantly higher levels of DNA damage, increased p53 activity, and a greater percentage of apoptotic cells were observed in SH-SY5Y cells transfected with G93A SOD1 when compared to cells overexpressing wild-type SOD1 and untransfected cells. Western blot, FACS, and confocal microscopy analysis demonstrated that G93A SOD1 is present in the nucleus in association with DNA. Nuclear G93A SOD1 has identical superoxide dismutase activity but displays increased peroxidase activity when compared to wild-type SOD1. These results indicate that the G93A mutant SOD1 association with DNA might induce DNA damage and trigger the apoptotic response by activating p53. This to...Continue Reading

References

Dec 1, 1988·The Journal of Cell Biology·L Y ChangJ D Crapo
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·S RabizadehD E Bredesen
Aug 16, 1994·Proceedings of the National Academy of Sciences of the United States of America·D R BorcheltD W Cleveland
Apr 29, 1998·Journal of the Neurological Sciences·F R WiedemannW S Kunz
Feb 15, 2000·The Journal of Biological Chemistry·M R CirioloG Rotilio
Oct 18, 2000·Free Radical Biology & Medicine·M BogdanovM Cudkowicz
Jul 19, 2002·Nature·Hilal A LashuelPeter T Lansbury
Aug 18, 2004·Trends in Molecular Medicine·Caterina Bendotti, Maria Teresa Carrì
Jul 21, 2005·Free Radical Research·Norberto AguirreMikhail B Bogdanov
Jul 22, 2005·Lancet Neurology·Sivakumar Sathasivam, Pamela J Shaw
Feb 14, 2006·Current Neurology and Neuroscience Reports·Peter M Andersen
Apr 11, 2006·Molecular Neurobiology·Sandra R BacmanCarlos T Moraes
May 23, 2006·Biochimica Et Biophysica Acta·Siân C BarberPamela J Shaw
Sep 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Alberto FerriMaria Teresa Carrì
May 17, 2007·Human Molecular Genetics·Daniela SauAngelo Poletti
May 17, 2007·IUBMB Life·Danilo B MedinasOhara Augusto
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Dairín KieranJochen H M Prehn
Feb 20, 2008·Mutagenesis·Andrew R CollinsRudolf Stetina
Mar 29, 2008·Antioxidants & Redox Signaling·Mauro CozzolinoMaria Teresa Carrì
Aug 1, 2008·Accounts of Chemical Research·Jean CadetJean-Luc Ravanat

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Citations

Nov 4, 2011·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Joanna Iłżecka
Nov 30, 2011·TheScientificWorldJournal·Fabio Coppedè
Nov 28, 2013·Advances in Medical Sciences·D MahovicM Bosnar-Puretic
May 23, 2015·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Renaid B KimCassie S Mitchell
Aug 11, 2015·Mutation Research·Fabio Coppedè, Lucia Migliore
May 31, 2011·Biochimica Et Biophysica Acta·Johannes EversePenelope W Coates
Jun 2, 2016·Cellular and Molecular Life Sciences : CMLS·Rebecca A JacksonEe Sin Chen
Sep 9, 2017·Molecular Neurobiology·Aline A BrasilElis C A Eleutherio
Oct 17, 2018·International Journal of Molecular Sciences·Anna Konopka, Julie D Atkin
May 28, 2019·Journal of Clinical Medicine·Matteo BordoniCristina Cereda
Mar 21, 2018·Neural Regeneration Research·Diane PenndorfAlexandra Kretz
Jan 24, 2021·Experimental & Molecular Medicine·Sung Min SonDavid C Rubinsztein
Jun 27, 2021·Cellular and Molecular Life Sciences : CMLS·Jannigje Rachel KokLaura Ferraiuolo
Aug 26, 2017·Aging and Disease·Aleksandra Szybińska, Wiesława Leśniak
Aug 12, 2021·Chemical Research in Toxicology·Peter S Spencer, Glen E Kisby

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