Homocysteine induces cytoskeletal remodeling and production of reactive oxygen species in cultured cortical astrocytes

摘要: Homocysteine (Hcy) is an excitatory amino acid which markedly enhances the vulnerability of neuronal cells to excitotoxicity and oxidative injury. Patients with severe hyperhomocysteinemia exhibit a wide range clinical manifestations including neurological abnormalities such as mental retardation, cerebral atrophy, seizures. In this study we treated cortical astrocytes neurons in culture 10 100 μM Hcy after 24 h exposure cytoskeletal remodeling was analyzed by immunocytochemistry. We observed dramatically altered actin cytoskeleton exposed Hcy, concomitant change morphology fusiform and/or flattened retracted cytoplasm. Moreover, disruption glial fibrillary acidic protein (GFAP) meshwork, supporting misregulation cytoskeleton. Induction reactive oxygen species (ROS) showed fluctuating levels along both concentrations. Actin induced prevented antioxidants folate (5 μM) or trolox (80 μM). Unlike astrocyte cytoskeleton, results evidence little susceptibility neuron until treatment, since immunocytochemical analysis that Hcy-treated presented unaltered neurite arborization. alterations viability were not Hcy. Neuron/astrocyte co-cultures anchorage dependence for survival over long Taken together, these findings indicate, astrocytes, but culture, target effects are mediated redox signaling. Astrocytes able respond (100 reorganizing their surviving, protecting from damage. Moreover our suggest protective role cytoskelon, probably generating signals would assure response damage