Lipid peroxidation associated protein damage in rat brain crude synaptosomal fraction mediated by iron and ascorbate

In crude synaptosomal fractions from rat brain exposed to iron and ascorbat e, enhanced lipid peroxidation (more than 3-fold compared to control), loss of protein thiols up to the extent of 40% compared to control, increased i ncorporation of carbonyl groups into proteins (more than 4.5-fold compared to control) and non-disulphide covalent cross-linking of membrane proteins have been observed. The phenomena are not inhibited by catalase or hydroxyl radical scavengers like mannitol or dimethyl sulphoxide. However. chain br eaking antioxidants like alpha -tocopherol and butylated hydroxytoluene pre vent both lipid peroxidation and accompanying protein oxidation. It is sugg ested that in this system lipid peroxidation propagated by the decompositio n of preformed lipid hydroperoxides by iron and ascorbate is the primary ev ent and products of the peroxidation process cause secondary protein damage . In view of high ascorbate content of brain and availability of several tr ansition metals. such ascorbate mediated oxidative damage may be relevant i n the aetiopathogenesis of several neurodegenerative disorders as well as a geing of brain. (C) 2001 Elsevier Science Ltd. All rights reserved.