4-Hydroxynonenal, or 4-hydroxy-2E-nonenal or 4-hydroxy-2-nonenal or 4-HNE or HNE, (C9H16O2), is an α,β-unsaturated hydroxyalkenal that is produced by lipid peroxidation in cells. 4-HNE is the primary α, β-unsaturated hydroxyalkenal formed in this process. It is a colorless oil. It is found throughout animal tissues, and in higher quantities during oxidative stress due to the increase in the lipid peroxidation chain reaction, due to the increase in stress events. 4-HNE has been hypothesized to play a key role in cell signal transduction, in a variety of pathways from cell cycle events to cellular adhesion. There seems to be a dual and hormetic action of 4-HNE on the health of cells: lower intracellular concentrations (around 0.1-5 mM) seem to be beneficial to cells, promoting proliferation, differentiation, antioxidant defense and compensatory mechanism, while higher concentrations (around 10-20 mM) have been shown to trigger well-known toxic pathways such as the induction of caspase enzymes, the laddering of genomic DNA, the release of cytochrome c from mitochondria, with the eventual outcome of cell death (through both apoptosis and necrosis, depending on concentration). HNE has been linked to the pathology of several diseases such as Alzheimer's disease, cataract, atherosclerosis, diabetes and cancer.
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