Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro

Üllen, Andreas; Fauler, Günter; Bernhart, Eva; Nusshold, Christoph; Reicher, Helga; Leis, Hans Jörg; Malle, Ernst; Sattler, Wolfgang

doi:10.1016/j.freeradbiomed.2012.08.575

Cited by 42 publications

(52 citation statements)

References 52 publications

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“…6). Interestingly, trapping of long chain aldehydes with phloretin (Ullen et al, 2012) also reduced LPS-induced H3/H4 histone acetylation (Fig 9). Further, exogenous addition of Δ 2 -hexadecenal to nuclear preparations from MLE-12 cells stimulated H3/H4 histone acetylation (data not shown), indicating a role for hexadecenal released from S1P could be a modulator of histone acetylation and inflammation.…”

Section: Mechanism(s) Of Lps-mediated Enhanced Nuclear Histone H3/h4 mentioning

confidence: 90%

Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase

Ebenezer

Suryadevara

et al. 2017

Advances in Biological Regulation

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Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation.

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Section: Mechanism(s) Of Lps-mediated Enhanced Nuclear Histone H3/h4 mentioning

confidence: 90%

Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase

Ebenezer

Suryadevara

et al. 2017

Advances in Biological Regulation

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“…Similarly, under oxidative conditions in vivo, D-chloroaldehydes can be converted to the corresponding acid form. These can be analysed by conversion to the PFB ester, and the derivative analysed using GC with NICI-MS [97]. Alternatively, direct analysis by liquid chromatography mass spectrometry (LC-MS) using 2-Cl-[d4]HA as an internal standard can be carried out [98].…”

Section: Analysis Of Free Aldehydic Oxidation Products and Their Metamentioning

confidence: 99%

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

145

105

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The process of lipid oxidation generates a diverse array of small aldehydes and carbonyl-containing compounds, which may occur in free form or esterified within phospholipids and cholesterol esters. These aldehydes mostly result from fragmentation of fatty acyl chains following radical oxidation, and the products can be subdivided into alkanals, alkenals (usually D,β-unsaturated), γ-substituted alkenals and bis-aldehydes.Isolevuglandins are non-fragmented di-carbonyl compounds derived from H 2 -isoprostanes, and oxidation of the ω-3-fatty acid docosahexenoic acid yield analogous 22 carbon neuroketals. Non-radical oxidation by hypochlorous acid can generate D-chlorofatty aldehydes from plasmenyl phospholipids. Most of these compounds are reactive and have generally been considered as toxic products of a deleterious process. The reactivity is especially high for the D,β-unsaturated alkenals, such as acrolein and crotonaldehyde, and for γ-substituted alkenals, of which 4-hydroxy-2-nonenal and 4-oxo-2-nonenal are best Page | 2 known. Nevertheless, in recent years several previously neglected aldehydes have been investigated and also found to have significant reactivity and biological effects; notable examples are 4-hydroxy-2-hexenal and 4-hydroxy-dodecadienal. This has led to substantial interest in the biological effects of all of these lipid oxidation products and their roles in disease, including proposals that HNE is a second messenger or signalling molecule.However, it is becoming clear that many of the effects elicited by these compounds relate to their propensity for forming adducts with nucleophilic groups on proteins, DNA and specific phospholipids. This emphasizes the need for good analytical methods, not just for free lipid oxidation products but also for the resulting adducts with biomolecules. The most informative methods are those utilizing HPLC separations and mass spectrometry, although analysis of the wide variety of possible adducts is very challenging. Nevertheless, evidence for the occurrence of lipid-derived aldehyde adducts in biological and clinical samples is building, and offers an exciting area of future research. AbbreviationsAcr-dG, 1,N2-propanodeoxyguanosine; AGEs, advanced glycation end-product; ALEs, advanced lipoxidation end product; ApoB100, apolipoprotein B100; ApoE, apolipoprotein E; ARP, aldehyde reactive probe; AspN, endoproteinase AspN (flavastacin); βLG, β-lactoglobulin; BHZ, biotin hydrazide; BN-PAGE, blue native polyacrylamide gel

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“…Production of α-ClFALD has been shown in human atherosclerotic plaques (5) and infarcted rat myocardium (6). MPO-derived α-ClFALD has also been implicated in endothelial dysfunction (7), neuronal apoptosis (8), activating the nuclear factor κB pathway, eNOS inhibition (9), neutrophil chemotaxis (3), and myocardial contractile dysfunction (6). Recently, α-ClFALD was also found in the lungs of mice and rats exposed to chlorine gas (Cl 2 ) along with its GSH adduct (FALD-GSH) and it was found to contribute to increased lung inflammation and permeability as well as systemic loss of eNOS-dependent vasodilation (10).…”

Section: Introductionmentioning

confidence: 99%

Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

Duerr

Palladino

Hartman

et al. 2018

Journal of Lipid Research

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Running Title: Bromofatty aldehyde modifications of glutathione and proteinAbbreviations: 2-bromohexadecanal (2-BrHDA), 2-bromohexadec-15-ynal (2-BrHDyA), 2-bromooctadecanal (2-BrODA), 2-chlorohexadecanal (2-ClHDA), 2-chlorohexadec-15-ynal (2-ClHDyA), 2-chlorooctadecanal (2-ClODA), α-chlorofatty aldehydes (α-ClFALD), α-bromofatty aldehydes (α- 2 ABSTRACT: α-Chlorofatty aldehydes (α-ClFALD) and α-bromofatty aldehydes (α-BrFALD) are produced in activated neutrophils and eosinophils. This study investigated the ability of α-BrFALD and α-ClFALD to react with the thiols of GSH and protein cysteinyl residues. Initial studies showed 2-bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared to 2-ClHDA as precursor. NaBr supplemented PMA-activated neutrophils formed more α-BrFALD and FALD-GSH compared to non-NaBr supplemented neutrophils. Primary human eosinophils, which preferentially produce HOBr and α-BrFALD accumulated FALD-GSH following PMA stimulation. Mice exposed to Br 2 gas had increased levels of both α-BrFALD and FALD-GSH in the lungs as well as elevated systemic plasma levels of FALD-GSH in comparisons to mice exposed to air. Similar relative reactivity of α-ClFALD and α-BrFALD with protein thiols was shown using click analogs of these aldehydes. Collectively, these data demonstrate GSH and protein adduct formation is much greater as a result of nucleophilic attack of cysteinyl residues on α-BrFALD compared to α-ClFALD, which was observed in both primary leukocytes and in mice exposed to bromine gas.

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Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro

Cited by 42 publications

References 52 publications

Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase

Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

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