Effects of reactive oxygen species on brain synaptic plasma membrane Ca2+-ATPase
Abstract
The regulation of free intracellular calcium [Ca2+]i is altered in neurons from the aged brain, possibly due to reductions in the activity of Ca2+ transporters. The plasma membrane Ca(2+)-ATPase (PMCA) plays a critical role in Ca2+ homeostasis, and its kinetic properties change in aged rat brain. These changes could be due to oxidative modification of PMCA as a result of age-related chronic oxidative stresses. The present studies were undertaken to determine the sensitivity of the neuronal PMCA to in vitro exposure of synaptic plasma membranes (SPMs) to reactive oxygen species (ROS). We examined the effects of three oxidants including peroxyl radicals generated by azo-initiators, 2,2'-Azobis 2-amidinopropane dihydrochloride (AAPH) and 4,4'-Azobis 14-cyanovaleric acid (ACVA), hydrogen peroxide (H2O2), and peroxynitrite (ONOO-). Synaptic plasma membranes briefly exposed to these oxidants were analyzed for functional and structural alterations in PMCA. Although all three oxidants led to significant loss of PMCA activity, the effect of ONOO- was the most potent, followed by peroxyl radicals and H2O2. Kinetic analysis of PMCA activity after oxidant treatment showed decreases in Vmax without significant changes in K(act). Immunoblots revealed oxidant-induced cross-linking of PMCA molecules that were partially reversed under reducing conditions and completely reversed with addition of urea. The PMCA appears to be very sensitive to inhibition by ROS and hence may be a target of oxida…
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Activated microglia may cause oxidative damage to neighboring neurons through the diffusion of ONOO−, which is known to induce structural and functional alterations of synapse components.
“the extensive formation of Ntyr in microglia suggests that activated microglia may cause oxidative damage to neighboring neurons through the diffusion of ONOO Ϫ , which is known to induce structural and functional alterations of synapse components (Zaidi and Michaelis, 1999).”
From Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase (2008) · cites this paper as Zaidi and Michaelis, 1999
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Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase
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- Authors
- Zaidi, A., & Michaelis, M. L.
- Affiliations
- University of Kansas (US)
- Corresponding author
- Michaelis, Mary L.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 27
- Issue
- 7-8
- Pages
- 810-821
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2062311940
- Cited by
- 154
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 6 · 2019: 4 · 2018: 3 · 2017: 8 · 2016: 2 · 2015: 9 · 2014: 5 · 2013: 7 · 2012: 8
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG12993, P01AG012993)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- plasma membrane Ca2+-ATPase, reactive oxygen species, oxidative stress, synaptic plasma membrane, brain aging, intracellular calcium homeostasis, peroxynitrite, hydrogen peroxide, peroxy radicals, AAPH, enzyme inhibition, protein cross-linking
- MeSH terms
- Calcium-Transporting ATPases, Age Factors, Amidines, Animals, Azo Compounds, Brain, Calcium, Hydrogen Peroxide, Kinetics, Male, Nitrates, Phenylhydrazines, Synaptic Membranes, Tyrosine, Urea, Valerates, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Rats
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