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Peroxynitrite‐Induced Alterations in Synaptosomal Membrane Proteins
Author(s) -
Koppal Tanuja,
Drake Jennifer,
Yatin Servet,
Jordan Brad,
Varadarajan Sridhar,
Bettenhausen Lori,
Butterfield D. Allan
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720310.x
Subject(s) - peroxynitrite , chemistry , synaptosome , biochemistry , membrane protein , biophysics , membrane , neuroscience , microbiology and biotechnology , biology , enzyme , superoxide
: Peroxynitrite (ONOO ‐ ) is a highly reactive,oxidizing anion with a half‐life of <1 s that is formed by reaction ofsuperoxide radical anion with nitric oxide. Several reports ofONOO ‐ ‐induced oxidation of lipids, proteins, DNA, sulfhydryls, andinactivation of key enzymes have appeared. ONOO ‐ has also beenimplicated as playing a role in the pathology of several neurodegenerativedisorders, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis,among others. Continuing our laboratory's interest in free radical oxidativestress in brain cells in AD, the present study was designed to investigate thedamage to brain neocortical synaptosomal membrane proteins and theoxidation‐sensitive enzyme glutamine synthetase (GS) caused by exposure toONOO ‐ . These synaptosomal proteins and GS have previously beenshown by us and others to have been oxidatively damaged in AD brain and alsofollowing treatment of synaptosomes with amyloid β‐peptide. The resultsof the current study showed that exposure to physiological levels ofONOO ‐ induced significant protein conformational changes,demonstrated using electron paramagnetic resonance in conjunction with aprotein‐specific spin label, and caused oxidation of proteins, measured by theincrease in protein carbonyls. ONOO ‐ also caused inactivation of GSand led to neuronal cell death examined in a hippocampal cell culture system.All these detrimental effects of ONOO ‐ were successfully attenuatedby the thiol‐containing antioxidant tripeptide glutathione. This researchshows that ONOO ‐ can oxidatively modify both membranous andcytosolic proteins, affecting both their physical and chemical nature. Thesefindings are discussed with reference to the potential involvement ofONOO ‐ in AD neurodegeneration.