Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease

Williams, Taufika Islam; Lynn, Bert C.; Markesbery, William R.; Lovell, Mark A.

doi:10.1016/j.neurobiolaging.2005.06.004

Cited by 354 publications

(280 citation statements)

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“…Recently, HPLC coupled with ESI/tandem mass spectroscopy was used to measure HNE and acrolein in several brain regions from patients affected by mild cognitive disorder and early Alzheimer ' s disease. These studies demonstrated increased levels of HNE and acrolein 66 in the brain tissue in both neurological disorders, indicating that lipid peroxidation occurs early in the pathogenesis of Alzheimer ' s disease. 66 While generation of HNE has been demonstrated by our group 24 , 29 and others, 67 , 68 to the best of our knowledge no study has examined free acrolein formation in brain tissue after stroke.…”

Section: Mass Spectroscopy and Lipid Peroxidation Productsmentioning

confidence: 81%

“…These studies demonstrated increased levels of HNE and acrolein 66 in the brain tissue in both neurological disorders, indicating that lipid peroxidation occurs early in the pathogenesis of Alzheimer ' s disease. 66 While generation of HNE has been demonstrated by our group 24 , 29 and others, 67 , 68 to the best of our knowledge no study has examined free acrolein formation in brain tissue after stroke. Recently, elevated levels of an acrolein-protein conjugate ( N ⑀ -(3-formyl-3,4-dehydropiperidino)-lysine, FDP-lysine) 61 , 69 were demonstrated in plasma of stroke patients using ACR-Lysine Adduct ELISA System (NOF Corporation, Tokyo, Japan).…”

Section: Mass Spectroscopy and Lipid Peroxidation Productsmentioning

confidence: 81%

“…66 Beyond damage to membranes, lipid peroxides give rise to reactive ␣ , ␤ -unsaturated aldehydes, including HNE and acrolein. These aldehydes covalently bind to proteins through reaction with thiol groups.…”

Section: Mass Spectroscopy and Lipid Peroxidation Productsmentioning

confidence: 99%

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Lipids and lipidomics in brain injury and diseases

Adibhatla

Hatcher

Dempsey

2006

AAPS J

145

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Lipidomics is systems-level analysis and characterization of lipids and their interacting moieties. The amount of information in the genomic and proteomic fi elds is greater than that in the lipidomics fi eld, because of the complex nature of lipids and the limitations of tools for analysis. The main innovation during recent years that has spurred advances in lipid analysis has been the development of new mass spectroscopic techniques, particularly the " soft ionization " techniques electrospray ionization and matrix-assisted laser desorption/ionization. Lipid metabolism may be of particular importance for the central nervous system, as it has a high concentration of lipids. The crucial role of lipids in cell signaling and tissue physiology is demonstrated by the many neurological disorders, including bipolar disorders and schizophrenia, and neurodegenerative diseases such as Alzheimer ' s, Parkinson ' s, and Niemann-Pick diseases, that involve deregulated lipid metabolism. Altered lipid metabolism is also believed to contribute to cerebral ischemic (stroke) injury. Lipidomics will provide a molecular signature to a certain pathway or a disease condition. Lipidomic analyses (characterizing complex mixtures of lipids and identifying previously unknown changes in lipid metabolism) together with RNA silencing, using small interfering RNA (siRNA), may provide powerful tools to elucidate the specifi c roles of lipid intermediates in cell signaling and open new opportunities for drug development.K e yw o r ds: Acrolein , arachidonic acid , cerebral ischemia , cytidine-5 ′ -diphosphocholine , CDP-choline , citicoline , docosahexaenoic acid , 4-hydroxynonenal , lipidomics , lipid peroxidation , MALDI-TOF , ESI-MS-MS , neuroprotectin D1 , 10,17S-docosatriene , phospholipases , phospholipids , RNA silencing , small interfering RNA , siRNA , reactive oxygen species , stroke INTRODUCTIONPhospholipids are important components of all mammalian cells and have a variety of biological functions: (1) they form lipid bilayers that provide structural integrity necessary for protein function, (2) they function as an energy reservoir (eg, triglycerides), and (3) they serve as precursors for various second messengers such as arachidonic acid, docosahexaenoic acid, ceramide, 1,2-diacylglycerol, phosphatidic acid, and lyso-phosphatidic acid. A deeper knowledge of the complexity of phospholipid metabolism will elevate our understanding of the role of lipids in maintaining normal cell physiology and how alterations in lipid metabolism contribute to various disease states. DEFINING A LIPIDLipids comprise an enormous number of chemically distinct molecules arising from combinations of fatty acids with various backbone structures. Indeed, it is diffi cult to defi ne what lipids are. Defi ning lipids as a class of biological molecules that share a high degree of solubility in organic solvents is considered at once too broad and too narrow, encompassing structurally and functionally unrelated molecules and excluding lipids, such as ganglioside...

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Section: Mass Spectroscopy and Lipid Peroxidation Productsmentioning

confidence: 81%

Section: Mass Spectroscopy and Lipid Peroxidation Productsmentioning

confidence: 81%

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Lipids and lipidomics in brain injury and diseases

Adibhatla

Hatcher

Dempsey

2006

AAPS J

145

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“…Levels of HNE are elevated in Alzheimer's disease brains and amyotrophic lateral sclerosis spinal cords (Pedersen et al, 1998;Volkel et al, 2006;Williams et al, 2006). Exposure of cultured neurons to HNE triggers cell death via LMP (Castino et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Zinc and 4-Hydroxy-2-Nonenal Mediate Lysosomal Membrane Permeabilization Induced by H₂O₂in Cultured Hippocampal Neurons

Hwang¹,

Lee²,

Kim³

et al. 2008

J. Neurosci.

136

118

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Lysosomal membrane permeabilization (LMP) is implicated in cancer cell death. However, its role and mechanism of action in neuronal death remain to be established. In the present study, we investigate the function of cellular zinc in oxidative stress-induced LMP using hippocampal neurons. Live-cell confocal microscopy with FluoZin-3 fluorescence showed that H 2 O 2 exposure induced vesicles containing labile zinc in hippocampal neurons. Double staining with LysoTracker or MitoTracker disclosed that the majority of the zinccontaining vesicles were lysosomes and not mitochondria.

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“…Several studies have shown that when the oxidative stress is induced by several agents, brain cells like microglia and astrocytes release diverse inflammatory mediators. 24,25 Moreover, oxidative stress indicators [reactive oxygen species (ROS), reactive lipid peroxidation products] act as critical signaling molecules to trigger inflammatory responses in the CNS through activation of redox sensitive transcription factors. 26,27 The ability of HNE to exert a number of toxicological effects has been attributed to its electrophilic α, β-unsaturated carbonyl moiety that can react through 1, 2 and 1, 4 additions with nucleophiles such as cysteine, lysine, and histidine residues.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Lipid Peroxidation Product 4-Hydroxynonenal on Neuroinflammation in Microglial Cells: Protective Role of Quercetin and Monochloropivaloylquercetin

Cumaoğlu

Agkaya

Ozkul

2019

tjps

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Objectives:The lipid peroxidation-derived aldehyde 4-hydroxynonenal (HNE) has been implicated in a number of oxidative stress-induced inflammatory pathologies such as neurodegenerative diseases and aging. In this regard, we investigated the effects of HNE on neuroinflammatory responses by measuring cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) induction with cytokine production. In addition, we measured nuclear factor erythroid 2-related factor 2 (Nrf-2)/Kelch-like ECH-associated protein 1 (Keap1) signaling proteins, and antioxidant enzymes heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1), and compared the results with quercetin and monochloropivaloylquercetin (MPQ) pretreated microglial cells. Materials and Methods: Cytotoxicity was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and production of cytokines was determined by cytokine array. Furthermore, intracellular Nfr2/Keap1 signaling proteins, HO-1, NQO1, and COX-2 expression were analyzed by western blot in 2.5 μM HNE treated BV-2 cells. Results: Inducible nitric oxide synthase (iNOS) and COX-2 mRNA levels were measured with reverse transcription-quantitative polymerase chain reaction. HNE induced both COX-2 mRNA and protein levels, iNOS mRNA expression, and cytokine production. In addition, HNE markedly increased Keap1 levels and decreased cytoplasmic Nrf-2 expression with antioxidant enzyme HO-1 levels. Quercetin and monochloropivaloylquercetin treatment alleviated neuroinflammatory responses in microglial cells, by decreasing COX-2 mRNA expression. Monochloropivaloylquercetin decreased cytoplasmic Keap1 levels and increased nuclear translocation of Nrf-2 resulted in induction of HO-1 and NQO1 expression. Conclusion: These results suggest that HNE could be a link between oxidative stress and inflammation in BV-2 microglia cells. In particular, monochloropivaloylquercetin alleviated inflammation, probably by decreasing the expression of proinflammatory genes and strengthening the antioxidant defense system. Key words: 4-Hydroxynonenal, microglia, quercetin, inflammation, cyclooxygenase-2, hemeoxygenase-1 ÖZ Amaç: Lipit peroksidasyonu ürünü aldehit, 4-hidroinonenal (HNE), nörodejeneratif hastalıklar ve yaşlanma gibi oksidatif strese bağlı inflamatuvar patolojilerle ilişkilendirilmiştir. Bu bağlamda, HNE'nin nöroinflamatuvar cevap üzerine etkisini siklooksijenaz-2 (COX-2), indüklenebilir nitrik oksit sentaz (iNOS) ifadelenmeleri ve sitokin üretimi üzerinden incelenmiştir. Bunlara ek olarak, nükleer faktör eritroid 2-ilişkili faktör 2 (Nrf2)/ Kelch-benzeri ECH-ilişkili protein 1 (Keap1) sinyal proteinleri, antioksidan enzimler hemoksijenaz-1 (HO-1) ve nikotinamid adenin dinükleotit fosfat dehidrojenaz, kinon 1 (NQO1) ifadelenme düzeyleri ölçüldü ve sonuçlar kersetin ve monokloropivaloilkersetin uygulanan hücrelerle karşılaştırılmıştır. Gereç ve Yöntemler: Sitotoksisite MTT (3-(4,5-dimetiltiyazol-2-yl)-2,5-difeniltetrazolyum bromit) indirgenme y...

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Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease

Cited by 354 publications

References 55 publications

Lipids and lipidomics in brain injury and diseases

Lipids and lipidomics in brain injury and diseases

Zinc and 4-Hydroxy-2-Nonenal Mediate Lysosomal Membrane Permeabilization Induced by H₂O₂in Cultured Hippocampal Neurons

Effect of the Lipid Peroxidation Product 4-Hydroxynonenal on Neuroinflammation in Microglial Cells: Protective Role of Quercetin and Monochloropivaloylquercetin

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Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease

Cited by 354 publications

References 55 publications

Lipids and lipidomics in brain injury and diseases

Lipids and lipidomics in brain injury and diseases

Zinc and 4-Hydroxy-2-Nonenal Mediate Lysosomal Membrane Permeabilization Induced by H2O2in Cultured Hippocampal Neurons

Effect of the Lipid Peroxidation Product 4-Hydroxynonenal on Neuroinflammation in Microglial Cells: Protective Role of Quercetin and Monochloropivaloylquercetin

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Zinc and 4-Hydroxy-2-Nonenal Mediate Lysosomal Membrane Permeabilization Induced by H₂O₂in Cultured Hippocampal Neurons