hne

HNE is an acronym that can refer to several terms, but it is most widely used in biochemistry to denote 4-hydroxy-2-nonenal (4-HNE), a reactive aldehyde produced during lipid peroxidation of omega-6 polyunsaturated fatty acids.

Formation and chemical nature

4-HNE arises when reactive oxygen species attack membrane lipids, leading to the cleavage of lipid hydroperoxides and the generation of aldehydes such as 4-HNE. It is an α,β-unsaturated aldehyde, making it a potent electrophile capable of reacting with nucleophilic sites on biomolecules. In proteins, it commonly forms covalent adducts with cysteine, histidine, and lysine residues through Michael addition or Schiff base reactions.

Biological significance

4-HNE can influence cell signaling at low concentrations but is cytotoxic at higher levels. Its adducts can alter protein function, enzyme activity, and mitochondrial performance, and they can modulate gene expression and inflammatory responses. Elevated HNE-adduct formation has been implicated in aging processes and various diseases, including neurodegenerative disorders (such as Alzheimer’s and Parkinson’s diseases), cardiovascular disease, and complications of diabetes.

Detection and research use

Analytical approaches to study 4-HNE include measurement of HNE-protein adducts, HNE-albumin adducts, and free HNE using techniques like LC-MS/MS, gas chromatography–mass spectrometry, and immunoassays. In research and clinical contexts, 4-HNE serves as a biomarker of oxidative stress and lipid peroxidation, as well as a subject of investigation into cellular damage and protective mechanisms.

Other meanings

As an acronym, HNE can denote entities in other disciplines. This article primarily addresses the lipid-derived aldehyde, with recognition that context determines the intended meaning.