Malondialdehyde inhibits an AMPK-mediated nuclear translocation and repression activity of ALDH2 in transcription

Choi, Ji Woong; Kim, Jaehwan; Cho, Sung Chun; Ha, Moon Kyung; Song, Kye Yong; Youn, Hong Duk; Park, Sang Chul

doi:10.1016/j.bbrc.2010.11.131

Cited by 17 publications

(12 citation statements)

References 25 publications

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“…MDA reacts with DNA forming guanine derivatives, which in the transcribed DNA strand of expressed genes strongly inhibit RNA polymerase II [55]. MDA can also affect transcription through modification of aldehyde dehydrogenase 2—which in the nucleus plays an important role in transcription repression through its interaction with histone deacetylases—by inhibiting its nuclear translocation and its repressive activity in general transcription [56]. The great variability of nuclear reactions for HNE and MDA (Figures 4 , 6, 7, 8, 9) suggests that susceptibility for this effect of lipid peroxidation products may vary among cell subpopulations.…”

Section: Discussionmentioning

confidence: 99%

The link between intraneuronal N-truncated amyloid-β peptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism

Frackowiak

Mazur-Kolecka

Schanen

et al. 2013

acta neuropathol commun

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BackgroundAutism is a neurodevelopmental disorder of unknown etiopathogenesis associated with structural and functional abnormalities of neurons and increased formation of reactive oxygen species. Our previous study revealed enhanced accumulation of amino-terminally truncated amyloid-β (Aβ) in brain neurons and glia in children and adults with autism. Verification of the hypothesis that intraneuronal Aβ may cause oxidative stress was the aim of this study.ResultsThe relationships between neuronal Aβ and oxidative stress markers—4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA)—were examined in the frontal cortex from individuals aged 7–32 years with idiopathic autism or with chromosome 15q11.2-q13 duplications (dup(15)) with autism, and age-matched controls. Quantification of confocal microscopy images revealed significantly higher levels of neuronal N-truncated Aβ and HNE and MDA in idiopathic autism and dup(15)/autism than in controls. Lipid peroxidation products were detected in all mitochondria and lipofuscin deposits, in numerous autophagic vacuoles and lysosomes, and in less than 5% of synapses. Neuronal Aβ was co-localized with HNE and MDA, and increased Aβ levels correlated with higher levels of HNE and MDA.ConclusionsThe results suggest a self-enhancing pathological process in autism that is initiated by intraneuronal deposition of N-truncated Aβ in childhood. The cascade of events includes altered APP metabolism and abnormal intracellular accumulation of N-terminally truncated Aβ which is a source of reactive oxygen species, which in turn increase the formation of lipid peroxidation products. The latter enhance Aβ deposition and sustain the cascade of changes contributing to metabolic and functional impairments of neurons in autism of an unknown etiology and caused by chromosome 15q11.2-q13 duplication.

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Section: Discussionmentioning

confidence: 99%

The link between intraneuronal N-truncated amyloid-β peptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism

Frackowiak

Mazur-Kolecka

Schanen

et al. 2013

acta neuropathol commun

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“…In vitro and in vivo studies show that regulation of ALDH2 activity can affect cellular response to oxidative stress [8,9]. ALDH2 activity can be affected by gene regulation [10] or post-translational modifications [11][12][13]. For example, ALDH2 can be directly deacetylated by SIRT3 leading to enzymatic inactivation of ALDH2 [13].…”

Section: Introductionmentioning

confidence: 99%

Acetylation‐dependent regulation of mitochondrial ALDH2 activation by SIRT3 mediates acute ethanol‐induced eNOS activation

Xue

Meng

et al. 2011

FEBS Letters

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Edited by Stuart Ferguson Keywords:Aldehyde dehydrogenase 2 Acetylation Endothelial nitric-oxide synthase Ethanol Reactive oxygen species SIRT3 a b s t r a c tModerate alcohol consumption has beneficial effects on endothelial nitric-oxide synthase (eNOS) activation, which can engender an array of anti-atherogenic actions. Here we show that in human aortic endothelial cells (HAECs), rapid activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) mediates ethanol-induced eNOS activation by preventing reactive oxygen species (ROS) accumulation. Furthermore, activation of ALDH2 by ethanol is due to its hyperacetylation by SIRT3 inactivation. These data suggest that ethanol-induced eNOS activation in HAECs may be dependent on ALDH2 hyperacetylation by SIRT3 inactivation.

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“…36 Furthermore, the activity of mitochondrial aldehyde dehydrogenase 2 is enhanced by AMPK phosphorylation. 37 Cardiac remodeling entails alterations in the equilibrium between protein synthesis and degradation. Autophagy plays an important role in the degradation and recycling of macromolecules and cellular organelles and serves as a cell survival mechanism in starving cells.…”

Section: Finckenberg Et Al Caloric Restriction and Mitochondrial Remomentioning

confidence: 99%

Caloric Restriction Ameliorates Angiotensin II–Induced Mitochondrial Remodeling and Cardiac Hypertrophy

et al. 2012

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Abstract-Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction.Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5Ј AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. Key Words: hypertension Ⅲ hypertrophy Ⅲ caloric restriction Ⅲ renin-angiotensin system Ⅲ mitochondria Ⅲ oxidative stress T he normal adult heart mainly uses free fatty acids for energy. 1 In heart failure, a shift toward increased glycolysis and glucose oxidation takes place. 2 Metabolic remodeling and impaired substrate use contribute to cardiac dysfunction and participate in the transition of cardiac hypertrophy to heart failure. [1][2][3] Mitochondria are the major site of substrate oxidation. 4 Bugger et al 5 used mitochondrial proteome profiling and found numerous changes in mitochondrial protein levels in rats with pressure overload-induced heart failure. They also demonstrated that the defect found in cardiac oxidative capacity was attributed, at least in part, to a mitochondrial defect downstream of substrate-specific pathways. 5 Oxidative stress causes direct and irreversible oxidative damage to macromolecules and disrupts several key redoxdependent signal transduction pathways in the arterial wall. 6 Angiotensin (Ang) II induces reactive-oxygen species (ROS) formation via Ang II type 1 receptor stimulation through a protein kinase C-dependent mechanism. 7 Vascular NADPH oxidases catalyze the transfer of electrons from the c...

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Malondialdehyde inhibits an AMPK-mediated nuclear translocation and repression activity of ALDH2 in transcription

Cited by 17 publications

References 25 publications

The link between intraneuronal N-truncated amyloid-β peptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism

The link between intraneuronal N-truncated amyloid-β peptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism

Acetylation‐dependent regulation of mitochondrial ALDH2 activation by SIRT3 mediates acute ethanol‐induced eNOS activation

Caloric Restriction Ameliorates Angiotensin II–Induced Mitochondrial Remodeling and Cardiac Hypertrophy

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