engleski

Biomedical relevance of lipid peroxidation product 4-hydroxynonenal

Current theories regarding mechanisms of oxygen toxicity focus on production of highly reactive oxygen species (ROS) in excess of detoxification systems of the cells, tissues and entire organism. Oxidative stress could cause various acute as well as chronic diseases in almost every organic system and makes the pathological base for cardiovascular diseases, cancer and neurodegenerative diseases. Excess in ROS in tissues is accompanied by oxidative degradation of polyunsaturated fatty acids of membrane lipids resulting in production of highly reactive aldehydes which are proposed to be "second messengers" for the primary free radicals which initiated lipid peroxidation. The highly reactive aldehyde 4-hydroxynonenal (HNE) appears to be one of major cytotoxic products of lipid peroxidation that could be found in various tissues even under normal, physiological conditions. Although physiological role of HNE has not been clarified yet, it seems that HNE plays important role in cell growth control (regulation of essential processes like proliferation, differentiation, apoptosis and necrosis). Many findings suggest that modification of cell growth in vitro by HNE depends on the presence of cytokines such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) or transforming growth factor beta (TGF-beta). Unlike ROS, HNE has unique feature to remain stable, not rapidly metabolized, by binding to proteins. Such HNE-protein conjugates might be even required for biological activities of HNE and could be detected by the use of monoclonal antibodies. The use of immunohistochemistry suggests high importance of HNE in pathophysiology on diseases based on oxidative stress. Thus, HNE may become a clinically applicable marker of lipid peroxidation on one side and on the other it is likely that HNE will become one of the most attractive factors for those who search for a small and reactive molecular links between genomics and proteomics in physiology and pathology.

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nije evidentirano