engleski

4-Hydroxynoneal as second messenger of free radicals in the blood-brain barrier

Excess in production of reactive oxygen species (ROS) is considered to play important role in various pathologies, such as cardiovascular diseases, cancer, metabolic disorders, autoimmune disorders and (neuro)degenerative processes. Of particular relevance is aggressive process of lipid peroxidation, in particular of poly-unsaturated fatty acids (PUFA) in cellular membranous structures, which is a progressive, chain reaction of ROS production resulting in final disintegration of the membranes. The final products of lipid peroxidation, reactive aldehydes, are considered as “second toxic messengers of free radicals”. Among the end products of lipid peroxidation of particular relevance is 4- hydroxynonenal (HNE), which acts also as a growth regulating factor interfering with the effects of various cytokines. HNE-protein adducts were found to be present in brain tumors, in particular astrocytomas, showing the distribution pattern specific for each types of the tumor and positive correlation with the level of malignancy of these neoplasms. Of particular relevance might be findings of association of HNE-protein adducts with the tumor blood vessels, indicating that while HNE could be found physiologically in the blood vessel walls, its spread into the brain tissue might be associated with the development and progression of the tumor. Complementary to that, we have found HNE to be present in the blood-brain barrier (BBB) under pathological circumstances, such as relative hypoxia (reduced blood flow) or inflammation (sepsis). The presence of HNE in the BBB in vivo might alter the function of the barrier allowing not only exchange of substances otherwise reduced by the BBB but also progressive pathological circumstances allowing secondary brain tissue damage.

blood-brain barrier; HNE; CNS disorders

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