4-Hydroxynonenal, an aldehydic product of lipid peroxidation, impairs signal transduction associated with muscarinic acetylcholine and metabotropic glutamate receptors : Possible action on Gαq/11

Published on Nov 18, 2002in Journal of Neurochemistry4.87
· DOI :10.1046/j.1471-4159.1997.69020570.x
Emmanuelle M. Blanc9
Estimated H-index: 9
(UK: University of Kentucky),
Jeremiah F. Kelly4
Estimated H-index: 4
+ 2 AuthorsMark P. Mattson177
Estimated H-index: 177
(UK: University of Kentucky)
: Considerable data indicate that oxidative stress and membrane lipid peroxidation contribute to neuronal degeneration in an array of age-related neurodegenerative disorders. In contrast, the impact of subtoxic levels of membrane lipid peroxidation on neuronal function is largely unknown. We now report that 4-hydroxy-nonenal (HNE), an aldehydic product of lipid peroxidation, disrupts coupling of muscarinic cholinergic receptors and metabotropic glutamate receptors to phospholipase C-linked GTP-binding proteins in cultured rat cerebrocortical neurons. At subtoxic concentrations, HNE markedly inhibited GTPase activity, inositol phosphate release, and elevation of intracellular calcium levels induced by carbachol (muscarinic agonist) and (RS)-3,5-dihydroxyphenyl glycine (metabotropic glutamate receptor agonist). Maximal impairment of agonist-induced responses occurred within 30 min of exposure to HNE. Other aldehydes, including malondialdehyde, had little effect on agonist-induced responses. Antioxidants that suppress lipid peroxidation did not prevent impairment of agonist-induced responses by HNE, whereas glutathione, which is known to bind and detoxify HNE, did prevent impairment of agonist-induced responses. HNE itself did not induce oxidative stress. Immunoprecipitation-western blot analysis using an antibody to HNE-protein conjugates showed that HNE can bind to Gαq/11. HNE also significantly suppressed inositol phosphate release induced by aluminum fluoride. Collectively, our data suggest that HNE plays a role in altering receptor-G protein coupling in neurons under conditions of oxidative stress that may occur both normally, and before cell degeneration and death in pathological settings.
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Cited By124
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Kasthuri Bai Magalingam6
Estimated H-index: 6
(Nilai University),
Ammu Kutty Radhakrishnan21
Estimated H-index: 21
(International Medical University)
+ 1 AuthorsNagaraja Haleagrahara16
Estimated H-index: 16
(JCU: James Cook University)
Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer’s disease is characterized by the abnormal accumulation of extracellular amyloid-β plaques and intraneuronal neu...
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Adele Romano18
Estimated H-index: 18
(Sapienza University of Rome),
Gaetano Serviddio30
Estimated H-index: 30
(University of Foggia)
+ 4 AuthorsSilvana Gaetani29
Estimated H-index: 29
(Sapienza University of Rome)
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Estimated H-index: 1
C FosterThomas1
Estimated H-index: 1
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Bruce A. Citron30
Estimated H-index: 30
(KU: University of Kansas),
Syed Ameenuddin6
Estimated H-index: 6
+ 3 AuthorsBarry W. Festoff36
Estimated H-index: 36
Abstract Thrombin and membrane lipid peroxidation (MLP) have been implicated in various central nervous system (CNS) disorders from CNS trauma to stroke, Alzheimer's (AD) and Parkinson's (PD) diseases. Because thrombin also induces MLP in platelets and its involvement in neurodegenerative diseases we hypothesized that its deleterious effects might, in part, involve formation of MLP in neuronal cells. We previously showed that thrombin induced caspase-3 mediated apoptosis in motor neurons, via a ...
Published on Jun 20, 2015in Antioxidants & Redox Signaling5.83
Giuseppina Barrera29
Estimated H-index: 29
Stefania Pizzimenti24
Estimated H-index: 24
+ 8 AuthorsAlessio Lepore4
Estimated H-index: 4
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Estimated H-index: 17
(PGIMER: Post Graduate Institute of Medical Education and Research),
Pawan Gupta9
Estimated H-index: 9
(PGIMER: Post Graduate Institute of Medical Education and Research)
+ 2 AuthorsKeshav Thakur3
Estimated H-index: 3
(PGIMER: Post Graduate Institute of Medical Education and Research)
Abstract Smoking has been suggested as one of the risk factor for amyotrophic lateral sclerosis (ALS) development. In order to investigate whether adverse effects of cigarette smoke in ALS have any association with increase in oxidative stress, disease severity, lipid hydroperoxides (LPO) and superoxide dismutase-1 (SOD1) levels were measured in biofluids of smoker and never smoker ALS patients and clinically correlated. Serum and CSF from sporadic ALS patients ( n = 50) diagnosed with El Escori...
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Giuseppe Valacchi40
Estimated H-index: 40
Alessandra Pecorelli24
Estimated H-index: 24
+ 4 AuthorsJoussef Hayek23
Estimated H-index: 23
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Published on Sep 1, 2012in Neurochemical Research2.78
Smijin Soman4
Estimated H-index: 4
(CUSAT: Cochin University of Science and Technology),
P. K. Korah3
Estimated H-index: 3
(CUSAT: Cochin University of Science and Technology)
+ 2 AuthorsC.S. Paulose26
Estimated H-index: 26
(CUSAT: Cochin University of Science and Technology)
In the present study we investigate the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. We demonstrate significant cellular loss in hippocampus of epileptic rats, visualized through decreased TOPRO stained neurons. Impaired spatial memory was observed in epileptic rats after Radial arm maze test. Treatment with WS and WA has resulted in increased number of...
Published on Apr 1, 2012in Food Science and Biotechnology0.89
Jae-Hee Park10
Estimated H-index: 10
(Kyungnam University),
Gyeong-Im Jeon4
Estimated H-index: 4
(Kyungnam University)
+ 1 AuthorsEunju Park20
Estimated H-index: 20
(Kyungnam University)
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Emma Arnal12
Estimated H-index: 12
Cristina Peris-Martínez7
Estimated H-index: 7
+ 2 AuthorsFrancisco J. Romero37
Estimated H-index: 37
(Universidad Católica de Valencia San Vicente Mártir)
View next paperEvidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal apoptosis.