4-hydroxynonenal in the pathomechanisms of oxidative stress

Here we review the current knowledge on the biochemistry and molecular path ology of oxidative stress with specific regard to a major aldehydic end-pro duct stemming from peroxidation of biomembranes, that is 4-hydroxynonenal ( HNE), This multifunctional molecule, which derives from the most represente d class of polyunsaturated fatty acids in the membranes, is potentially abl e to undergo a number of reactions with proteins, phospholipids, and nuclei c acids. Despite an active metabolism in most of the cell types, HNE can be detected in several biological tissues by means of sufficiently precise me thods, although with different sensitivity. In particular, relatively high steady-state levels of HNE are often detectable in a large variety of human disease processes, pointing to some involvement of the aldehyde in their p athogenesis. Among the prominent pathobiochemical effects of HNE is its rem arkable stimulation of fibrogenesis and inflammation, which indicates a pot ential contribution of the aldehyde to the pathogenesis of several chronic diseases, whose progression is indeed supported by inflammatory reactions a nd characterized by fibrosis, Further, of interest appears to be the abilit y of HNE to modulate cell proliferation through interference with the activ ity of cyclins and protein kinases and with the apoptotic machinery. Finall y, on the basis of the already achieved evidence, pursuing investigation of the role of HNE in signal transduction and gene expression seems very prom ising.