Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients

Biochemical and Biophysical Research Communications
Kazuko Takahashi-NikiHiroyoshi Ariga

Abstract

DJ-1 is a multi-functional protein that plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in onset of Parkinson's disease. We have previously reported that L166P, a mutant DJ-1 found in Parkinson's disease patients, had no activity to prevent hydrogen peroxide (H2O2)-induced cell death. In this study, we analyzed other mutants of DJ-1 found in Parkinson's disease patients, including M26I, R98Q, and D149A, as well as L166P. We first found that all of the mutants made heterodimers with wild-type DJ-1, while all of the mutants except for L166P made homodimers. We then found that M26I and L166P, both of which are derived from homozygous mutations of the DJ-1 gene, were unstable and that their stabilities were recovered, in part, in the presence of proteasome inhibitor, MG132. NIH3T3 cell lines stably expressing these mutants of DJ-1 showed that cell lines of L166P and C106S, a mutant for protease activity (-) of DJ-1, had no activity to scavenge even endogenously producing reactive oxygen species. These cell lines also showed that all of the mutants had reduced activities to eliminate exogenously added H2O2 and that these activities, except for that of D149A, were par...Continue Reading

References

Feb 23, 1987·Life Sciences·W J NicklasR E Heikkila
Jan 29, 2002·Free Radical Research·A Mitsumoto, Y Nakagawa
May 7, 2002·EMBO Reports·Moran BenharAlexander Levitzki
Jul 12, 2002·Proteomics·Chantragan SrisomsapJisnuson Svasti
Jul 23, 2002·Biological & Pharmaceutical Bulletin·Masahiko OkadaHiroyoshi Ariga
May 17, 2003·Fertility and Sterility·Ashok AgarwalMohamed A Bedaiwy
Jul 29, 2003·Aging Cell·Tamara R GoldenSimon Melov
Sep 4, 2003·Annals of Neurology·Patrick M Abou-SleimanNicholas W Wood
Oct 28, 2003·Molecular Reproduction and Development·Kaoru YoshidaTeruaki Iwamoto
Dec 4, 2003·Biochemical and Biophysical Research Communications·Takanori YokotaHidehiro Mizusawa
Dec 10, 2003·Brain : a Journal of Neurology·Rina BandopadhyayAndrew J Lees
Jan 6, 2004·Annals of Neurology·Patrizia RizzuPeter Heutink
Jan 6, 2004·Annals of Neurology·Katja HedrichChristine Klein
Jan 30, 2004·EMBO Reports·Takahiro TairaHiroyoshi Ariga

❮ Previous
Next ❯

Citations

Nov 28, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Mariaelena RepiciFlaviano Giorgini
Jun 25, 2005·Cell Death and Differentiation·Y ShinboH Ariga
May 11, 2012·Journal of Biomolecular Structure & Dynamics·Calvin Yu-Chian Chen
Sep 4, 2010·Antioxidants & Redox Signaling·Mark A Wilson
Jan 22, 2010·Human Molecular Genetics·Chenere P RamseyBenoit I Giasson
Oct 14, 2010·Human Molecular Genetics·Kelly Jean ThomasMark R Cookson
Apr 23, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Yoshikuni MizunoHideki Mochizuki
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Christine Klein, Ana Westenberger
Jul 24, 2008·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Steven J MullettDavid A Hinkle
May 26, 2010·Neuropathology : Official Journal of the Japanese Society of Neuropathology·David A HinkleRonald L Hamilton
Nov 15, 2012·Molecular and Cellular Biology·Izumi KatoHiroyoshi Ariga
Jun 15, 2005·Annual Review of Biochemistry·Mark R Cookson
Jul 19, 2005·Annual Review of Neuroscience·Darren J MooreTed M Dawson
Oct 13, 2010·Journal of Geriatric Psychiatry and Neurology·Lynn M BekrisCyrus P Zabetian
May 31, 2007·Molecular Neurodegeneration·Hiroo Yamaguchi, Jie Shen
Sep 9, 2010·Biological & Pharmaceutical Bulletin·Shi-Ping ZhangXiao-Ping Pu
Aug 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Marc C MeulenerNancy M Bonini
Mar 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Raymond H KimTak W Mak
Jun 13, 2014·Reproduction : the Official Journal of the Society for the Study of Fertility·Yi SunXiao-Ping Pu
Sep 5, 2015·Free Radical Research·Nelmi O Devarie-BaezCristina M Furdui
Oct 14, 2009·Biochemical and Biophysical Research Communications·Takuya HayashiSanae M M Iguchi-Ariga
Sep 21, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Daijiro YanagisawaHiroyoshi Ariga
Oct 21, 2015·Pharmacology & Therapeutics·Uma A MukherjeeDerek J Hausenloy
Sep 7, 2011·Journal of Structural Biology·Lakshmanane PremkumarStefan J Riedl
Mar 16, 2005·Cancer Cell·Raymond H KimTak W Mak
Dec 17, 2014·Biochemical Pharmacology·Ji CaoBo Yang
Nov 18, 2014·Antioxidants & Redox Signaling·Yuexin ShanClaudia C Dos Santos
Jun 6, 2009·Journal of Pharmacological Sciences·Wei QuHiroyoshi Ariga

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.