Disease relevance of trans-4-Hydroxy-2-nonenal

• Elevated levels of trans-4-hydroxy-2-nonenal (HNE) are observed in brain tissues in patients with neurodegenerative diseases [1].
• Acute toxicity of trans-4-hydroxy-2-nonenal in Fisher 344 rats [corrected] [2].
• Long-chain adducts of trans-4-hydroxy-2-nonenal to DNA bases cause recombination, base substitutions and frameshift mutations in M13 phage [3].

Psychiatry related information on trans-4-Hydroxy-2-nonenal

• Protein adducts of the lipid peroxidation product trans-4-hydroxy-2-nonenal (HNE) are features of oxidative damage in neuronal cell bodies in Alzheimer's disease but are also seen in axons of normal as well as diseased individuals [4].

High impact information on trans-4-Hydroxy-2-nonenal

• Other alkenals such as trans-4-hydroxy-2-nonenal have previously been isolated from microsomal systems when treated with halogenated hydrocarbons or subjected to lipid peroxidation [5].
• Trans-4-hydroxy-2-nonenal (4-HNE) is a major product of LPO, and its level becomes relatively high in cells under oxidative stress [6].
• Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis [6].
• Lipid peroxidation in biological membranes is known to yield reactive aldehydes, of which trans-4-hydroxy-2-nonenal (HNE) is particularly cytotoxic [7].
• Enantioselective metabolism of trans-4-hydroxy-2-nonenal by brain mitochondria [8].

Biological context of trans-4-Hydroxy-2-nonenal

• Astrocytic biotransformation of trans-4-hydroxy-2-nonenal is dose-dependent [1].
• Effect of enzyme-resistant starch on formation of 1,N(2)-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal and cell proliferation in the colonic mucosa of healthy volunteers [9].
• Our aim was to investigate, whether besides direct oxidative DNA damage, reactive oxygen and nitrogen species induce lipid peroxidation (LPO) that could yield etheno-DNA adducts via trans-4-hydroxy-2-nonenal, a major aldehyde generated by LPO, in colon tissue [10].
• We studied the effect of trans-4-hydroxy-2-nonenal on the wild-type human adenylosuccinate lyase and on the enzyme from a patient compound-heterozygous for two missense mutations (P75A/D397Y; McKusick 103050.0003/103050.0004) [11].

Anatomical context of trans-4-Hydroxy-2-nonenal

• The formation and toxicity of trans-4-hydroxy-2-nonenal in the central nervous system is well documented [12].
• Is the glutathione conjugate of trans-4-hydroxy-2-nonenal transported by the multispecific organic anion transporting-ATPase of human erythrocytes [13]?
• Trans-4-hydroxy-2-nonenal (4-HNE), a cytotoxic end product of lipid peroxidation, is present in normal human blood plasma at concentrations of 0.1-1.0 microM [13].

Associations of trans-4-Hydroxy-2-nonenal with other chemical compounds

• The epoxy aldehyde can be generated from trans-4-hydroxy-2-nonenal, a lipid peroxidation product of omega-6 polyunsaturated fatty acids, by autoxidation or by incubation with fatty acid hydroperoxides or hydrogen peroxides (Chem. Res. Toxicol., 9, 306) [14].
• Trans-4-hydroxy-2-nonenal (4-HNE), a major electrophilic by-product of lipid peroxidation, is able to interact with DNA to form exocyclic guanine adducts [15].
• A sensitive and selective capillary liquid chromatography nanoelectrospray isotope dilution mass spectrometric method was developed to identify and quantify the endogenous cyclic DNA adducts derived from trans-4-hydroxy-2-nonenal with 2'-deoxyguanosine (HNE-dG) in human brain tissues [16].
• Here we report for the first time the quantitation of glutathione conjugates of trans-4-hydroxy-2-nonenal (HNEGSH) in the human postmortem brain using the specific and very sensitive method of electrospray ionization triple quadrupole mass spectrometry (ESI-MS-MS) [17].
• Lipid peroxidation generates reactive aldehydes such as trans-4-hydroxy-2-nonenal and malonaldehyde, which form promutagenic exocyclic DNA adducts in human cells and may contribute to diet-related cancers [18].

Gene context of trans-4-Hydroxy-2-nonenal

• ALDH2 and other ALDHs are NAD(P)+-dependent enzymes critical to the detoxification of cytotoxic lipid-aldehydes elevated in atherosclerotic lesions, such as trans-4-hydroxy-2-nonenal (HNE) [19].
• We determined effects of the inflammation and oxidative stresses of tumor necrosis factor-alpha (TNFalpha) and trans-4-hydroxy-2-nonenal (HNE), respectively, on PTEN, Akt, and GSK3beta signalling in rat primary cortical neurons [20].
• In vivo involvement of cytochrome P450 4A family in the oxidative metabolism of the lipid peroxidation product trans-4-hydroxy-2-nonenal, using PPARalpha-deficient mice [21].
• The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma [15].
• In the present study, the methodology of flow cytometry was used to optimize quantification of the toxic effects of tumor necrosis factor-alpha (TNF-alpha), trans-4-hydroxy-2-nonenal (4-HNE), and aged amyloid-beta (Abeta1-42) on rat primary cortical neurons [22].

Analytical, diagnostic and therapeutic context of trans-4-Hydroxy-2-nonenal

• Detection and quantification of endogenous cyclic DNA adducts derived from trans-4-hydroxy-2-nonenal in human brain tissue by isotope dilution capillary liquid chromatography nanoelectrospray tandem mass spectrometry [16].

References