Role of 4-hydroxy-trans-2-nonenal in cell functions

Abstract

The role of lipid peroxidation product 4-hydroxy-trans-2-nonenal (4-HNE) in functional activity of cells under normal and different pathological conditions is discussed. Different pathways of 4-HNE metabolism in tissues are analyzed, with particular focus on the role the glutathione system in this process. 4-HNE is implicated in regulation of cell growth, proliferation, differentiation, and apoptosis. 4-HNE and metabolic products of other antioxidants (carotenoids) resemble each other in chemical nature of the product and influence general pathways of signal transduction. Manifestation of 4-HNE toxicity under oxidative stress conditions is regarded as a link to many diseases whose pathogenesis is connected with modifications of proteins and nucleic acids.

Compensatory renal hypertrophy and the handling of an acute nephrotoxicant in a model of aging

“…The formation of 4-HNE adducts is a reliable measurement of oxidative stress (Dubinina and Dadali 2010). The measured concentration of adducts (μg/mL) in the kidneys of young control rats was not significantly different from that in the remnant kidney of young NPX rats (Figure 3A).…”

Age-associated neurodegeneration and oxidative damage to lipids, proteins and DNA

“…Fatty acid peroxides can give rise to a variety of aldehydes. Among the generated aldehydes, 4-hydroxy-2-nonenal (HNE) is considered to be one of the most toxic that causes extensive damage and results in apoptosis (Dubinina and Dadali, 2010). HNE can be generated from ArAc or linoleic acid after being attacked by peroxides and due to the lipophilic characteristics of HNE it can easily be associated with membranes.…”

“…However, HNE is also capable of disintegrating membranes and is able to travel between cell components. HNE interacts with membranes and a wide array of amino acids residues that in receptors, chaperones, electron transport chain proteins and oxidative damage repairing proteins (Dubinina and Dadali, 2010;Farooqui and Horrocks, 2006).…”

Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA

“…Endogenously generated reactive electrophilic species act as redox-sensors that can affect the functioning of multiple molecules involved in the regulation of basic homeostatic mechanisms, including cell proliferation and apoptosis, energy metabolism and DNA damage-response. [8][9][10] Actions of these electrophiles that are most likely to be relevant to progression toward a cancer are ones elicited when they are generated at elevated, albeit non-toxic levels, and over a protracted period of time, a condition that can be identified by the presence of their protein adducts. The findings presented here provide a first glimpse of the wide-ranging molecular changes that might be associated with the presence of protein adducts of lipid peroxidation.…”

“…4HNE is a major, reactive end product of organic hydroperoxides generated as a consequence of free radical initiated oxidation of polyunsaturated fatty acids. [8][9][10] When the rate of production of 4HNE exceeds tissues' capacity to inactivate it, 4HNE forms immunoreactive adducts that persist, which makes them valuable in studies of chronic oxidative stress-associated diseases. [11][12][13][14] A critical role of oxidative stress in carcinogenesis is recognized.…”