脂质过氧化
免疫组织化学
光老化
生物化学
化学
活性氧
组氨酸
赖氨酸
半胱氨酸
癌症研究
氧化应激
生物
免疫学
氨基酸
酶
遗传学
作者
Kamelija Zarkovic,Antonia Jakovcevic,Neven Zarkovic
标识
DOI:10.1016/j.freeradbiomed.2016.12.009
摘要
Excessive production of reactive oxygen species can induce peroxidation of the polyunsaturated fatty acids thus generating reactive aldehydes like 4-hydroxy-2-nonenal (HNE), denoted as "the second messenger of free radicals". Because HNE has high binding affinity for cysteine, histidine and lysine it forms relatively stable and hardly metabolized protein adducts. By changing structure and function of diverse structural and regulatory proteins, HNE achieves not only cytotoxic, but also regulatory functions in various pathophysiological processes. Numerous animal model studies and clinical trials confirmed HNE as one of the crucial factors in development and progression of many disorders, in particular of cancer, (neuro)degenerative, metabolic and inflammatory diseases. Since HNE has multiple biological effects and is in the living system usually bound to proteins and peptides, many research groups work on development of specific immunochemical methods targeting the HNE-histidine adducts as major bioactive marker of lipid peroxidation, following the research pathway initiated by Hermann Esterbauer, who discovered HNE in 60's. Such immunohistochemical studies did not only prove the high biomedical importance of HNE, but have also given new insights into major diseases of the modern man. Immunohistochemical studies have shown reversibility of formation of the HNE-protein adducts, as well as differential onset of the HNE-mediated lipid peroxidation between age- associated atherosclerosis and photoaging, revealing eventually selective anti-cancer effects of HNE produced by non-malignant cells in vicinity of cancer. This review summarizes some of the HNE-histidine immunohistochemistry findings we believe are of broad biomedical interest and could inspire new studies in the field.
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