GAPDH is conformationally and functionally altered in association with oxidative stress in mouse models of amyotrophic lateral sclerosis.

Journal of Molecular Biology
Anson PierceAsish Chaudhuri

Abstract

It is proposed that conformational changes induced in proteins by oxidation can lead to loss of activity or protein aggregation through exposure of hydrophobic residues and alteration in surface hydrophobicity. Because increased oxidative stress and protein aggregation are consistently observed in amyotrophic lateral sclerosis (ALS), we used a 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (BisANS) photolabeling approach to monitor changes in protein unfolding in vivo in skeletal muscle proteins in ALS mice. We find two major proteins, creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), conformationally affected in the ALS G93A mouse model concordant with a 43% and 41% reduction in enzyme activity, respectively. This correlated with changes in conformation and activity that were detected in CK and GAPDH with in vitro oxidation. Interestingly, we found that GAPDH, but not CK, is conformationally and functionally affected in a longer-lived ALS model (H46R/H48Q), exhibiting a 22% reduction in enzyme activity. We proposed a reaction mechanism for BisANS with nucleophilic amino acids such as lysine, serine, threonine, and tyrosine, and BisANS was found to be primarily incorporated to lysine residues in GA...Continue Reading

References

Jan 1, 1992·Free Radical Research Communications·Y J SuzukiG D Ford
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·C C ChaoE R Stadtman
Apr 16, 1998·Methods in Enzymology·J W SealeP M Horowitz
Aug 10, 2000·Journal of the Neurological Sciences·M Said AhmedT Siddique
Jan 25, 2002·Annals of the New York Academy of Sciences·E R Stadtman
Apr 30, 2002·Free Radical Biology & Medicine·Silke WendtOle A Andreassen
May 29, 2002·Free Radical Biology & Medicine·Reshma Shringarpure, Kelvin J A Davies
May 24, 2003·Biochemical and Biophysical Research Communications·Tilman GruneKelvin J A Davies
Aug 2, 2003·Biochemical and Biophysical Research Communications·Elena I ArutyunovaVladimir I Muronetz
Aug 14, 2003·Biochemical and Biophysical Research Communications·E V SchmalhausenV I Muronetz
Jan 23, 2004·Organic & Biomolecular Chemistry·Nelly Khidekel, Linda C Hsieh-Wilson
Mar 1, 2006·Biochemistry·Anson PierceAsish Chaudhuri
Mar 3, 2006·Acta Crystallographica. Section D, Biological Crystallography·Jermaine L Jenkins, John J Tanner
Apr 4, 2006·Muscle & Nerve·Douglas J MahoneyMark A Tarnopolsky
Aug 1, 2006·Biochimica Et Biophysica Acta·Edor Kabashi, Heather D Durham
Sep 28, 2006·Mechanisms of Ageing and Development·Asish R ChaudhuriArlan Richardson
Oct 4, 2006·Molecular & Cellular Proteomics : MCP·Michael L NielsenRoman A Zubarev
Nov 9, 2006·Free Radical Research·Earl R Stadtman
Nov 9, 2006·Free Radical Research·Rebecca WidmerTilman Grune
Jun 23, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Florian L MullerHolly Van Remmen
Nov 27, 2007·Free Radical Biology & Medicine·Anson P PierceAsish R Chaudhuri

❮ Previous
Next ❯

Citations

Jun 5, 2010·Journal of Proteome Research·Ashraf G Madian, Fred E Regnier
Aug 2, 2011·Journal of Proteome Research·Ashraf G MadianFred E Regnier
Feb 6, 2013·Biochemistry. Biokhimii︠a︡·E I ArutyunovaV I Muronetz
Dec 3, 2014·Neurochemistry International·Mariarita GalbiatiAngelo Poletti
May 23, 2014·Journal of Proteomics·Kristin ElfKonstantin Artemenko
Jan 5, 2016·Nitric Oxide : Biology and Chemistry·Takeya KuboTadayoshi Takeuchi
May 23, 2015·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Renaid B KimCassie S Mitchell
Oct 24, 2012·Free Radical Biology & Medicine·Jennalynn StyskalAdam B Salmon
May 15, 2012·Free Radical Biology & Medicine·Zili ZhaiDario C Ramirez
Oct 6, 2010·Biochemical and Biophysical Research Communications·Anson PierceArlan Richardson
Oct 31, 2009·Biochemical and Biophysical Research Communications·Hidemitsu NakajimaTadayoshi Takeuchi
Aug 19, 2015·International Journal of Biological Macromolecules·Shao LiangZhang Ping
Nov 8, 2011·Free Radical Biology & Medicine·Jennalynn StyskalAdam B Salmon
Sep 5, 2013·Free Radical Biology & Medicine·André M N SilvaPedro Domingues
Apr 2, 2014·Biochemical and Biophysical Research Communications·Arunabh BhattacharyaAsish R Chaudhuri
May 17, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Arlan G Richardson, Eric E Schadt
Mar 21, 2013·International Braz J Urol : Official Journal of the Brazilian Society of Urology·Ana Júlia Vieira de RibeiroGilda Alves
May 7, 2020·Pharmaceutics·Vladimir F LazarevBoris A Margulis
Jan 18, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Yun ShiHolly Van Remmen
Sep 12, 2015·The Journal of Biological Chemistry·Masanori ItakuraTadayoshi Takeuchi
Mar 10, 2020·Oxidative Medicine and Cellular Longevity·Jeremiah Oshiomame Unuofin, Sogolo Lucky Lebelo
Nov 7, 2017·Frontiers in Molecular Neuroscience·Céline DesseilleFrédéric Charbonnier
Apr 11, 2021·Biogerontology·I AlmeidaA Nunes

❮ Previous
Next ❯

Related Concepts

Related Feeds

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.