The N-terminal copper-binding domain of the amyloid precursor protein protects against Cu2+ neurotoxicity in vivo

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Waldo CerpaNibaldo C Inestrosa

Abstract

The amyloid precursor protein (APP) contains a Cu binding domain (CuBD) localized between amino acids 135 and 156 (APP135-156), which can reduce Cu2+ to Cu1+ in vitro. The physiological function of this APP domain has not yet being established; nevertheless several studies support the notion that the CuBD of APP is involved in Cu homeostasis. We used APP synthetic peptides to evaluate their protective properties against Cu2+ neurotoxicity in a bilateral intra-hippocampal injection model. We found that human APP135-156 protects against Cu2+-induced neurotoxic effects, such as, impairment of spatial memory, neuronal cell loss, and astrogliosis. APP135-156 lacking two histidine residues showed protection against Cu2+; however, APP135-156 mutated in cysteine 144, a key residue in the reduction of Cu2+ to Cu1+, did not protect against Cu2+ neurotoxicity. In accordance with recent reports, the CuBD of the Caenorhabditis elegans, APL-1, protected against Cu2+ neurotoxicity in vivo. We also found that Cu2+ neurotoxicity is associated with an increase in nitrotyrosine immunofluorescence as well as with a decrease in Cu2+ uptake. The CuBD of APP therefore may play a role in the detoxification of brain Cu.

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·W WascoF Solomon
May 1, 1984·Journal of Neuroscience Methods·R Morris
Jul 25, 1994·FEBS Letters·L HesseG Multhaup
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·I Daigle, C Li
Jul 1, 1996·Chemical Research in Toxicology·J S Beckman
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·B Zhou, J Gitschier
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·J AraH Ischiropoulos
Aug 26, 1999·Journal of Neurochemistry·F H RuizN C Inestrosa
Aug 15, 2000·Annual Review of Nutrition·E D Harris
Dec 6, 2001·The Journal of Biological Chemistry·Jaekwon LeeDennis J Thiele
Jul 24, 2002·Biochemistry·Andreas SimonsGerd Multhaup
Sep 7, 2002·The Journal of Biological Chemistry·Christa J MaynardQiao-Xin Li
Feb 8, 2003·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Carlos OpazoNibaldo C Inestrosa
Apr 12, 2003·Trends in Neurosciences·Ashley I Bush
Sep 30, 2003·Molecular Psychiatry·M A ChacónN C Inestrosa

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Citations

Sep 6, 2008·Molecular Neurobiology·Daniela L RebolledoNibaldo C Inestrosa
Jan 7, 2011·Metallomics : Integrated Biometal Science·Ebany J Martinez-FinleyMichael Aschner
Jan 21, 2014·Progress in Neurobiology·Ivo F ScheiberRalf Dringen
Feb 9, 2012·Journal of Amino Acids·D Allan Butterfield, Rukhsana Sultana
May 11, 2012·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·R AldunateN C Inestrosa
Mar 19, 2011·Toxicology·Klaudia Jomova, Marian Valko
Jan 15, 2005·Progress in Neurobiology·Carlos MorganNibaldo C Inestrosa
Mar 26, 2009·Biochemical and Biophysical Research Communications·Miriam SuazoMauricio Gonzalez
Aug 23, 2005·Molecular Aspects of Medicine·Waldo CerpaNibaldo C Inestrosa
Nov 10, 2016·Ageing Research Reviews·Pu Wang, Zhan-You Wang
Oct 29, 2009·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ya Hui HungRobert Alan Cherny
Oct 6, 2005·IUBMB Life·Nibaldo C InestrosaLorena Varela-Nallar
Apr 22, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jie ZhangBao-Lu Zhao
Aug 24, 2019·Archives of Toxicology·Miriama SimunkovaMarian Valko
Dec 18, 2019·Current Pharmaceutical Design·Gesivaldo SantosDjalma M de Oliveira
Aug 24, 2010·Molecular and Cellular Biochemistry·Klaudia JomovaMarian Valko

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