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Lipid peroxidation end product as a modulator of cell growth

Oxidative stress caused by reactive oxygen species (ROS) is capable of disturbing the integrity of cell membranes via peroxidation of membrane lipids and alteration of the structure and function of macromolecules. Reactive aldehydes, in particular 4- hydroxynonenal (HNE), are endogenous end products resulting from the lipid peroxidation of polyunsaturated fatty acids of membrane lipids. For a long time, HNE has been considered as a mainly toxic product of lipid peroxidation, implicated in the pathophysiology of several diseases such as neurodegenerative diseases, ischemia/reperfusion states, atherosclerosis, diabetes and cancer. However, HNE is permanently formed also under physiological conditions, and has signaling activities in regulation of cell cycle, proliferation, differentiation and apoptosis. A complex network of signal cascades involving HNE is intensively studied. Various signaling pathways are directly or indirectly affected by HNE, because HNE is able to react with a number of cellular elements. Due to the strong affinity to bind to bioactive macromolecules, in particular proteins and peptides, HNE could modify their structure and consequently their function. Formation of HNE-cell surface protein adducts could mimic ligand-cell surface receptor binding, and induce activation of receptor-triggered signal transduction. Thus, HNE is considered also as a growth regulating factor, interfering with the cytokine activities. Interaction of HNE and other growth factors and their influence on cell proliferation will be topic of this article.

lipid peroxidation, 4-hydroxynonenal, growth factors, cytokines, 3H-thymidine incorporation, cell proliferation, EGF, IGF-1, bFGF

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