Hydrogen peroxide alters membrane and cytoskeleton properties and increases intercellular connections in astrocytes

Excess hydrogen peroxide (H₂O₂) is produced in the pathogenesis of brain injuries and neurodegenerative diseases. H₂O₂ may damage cells through direct oxidation of lipids, proteins and DNA or it can act as a signaling molecule to trigger intracellular pathways leading to cell death. In this study, H₂O₂ caused plasma membranes of primary astrocytes to become more gel-like, while artificial membranes of vesicles composed of rat brain lipid extract became more liquid crystalline-like. Besides the effects on membrane phase properties, H₂O₂ promoted actin polymerization, induced the formation of cell-to-cell tunneling nanotube (TNT)-like connections among astrocytes and increased the colocalization of myosin Va with F-actin. Myosin Va was also observed in the H₂O₂-induced F-actin-enriched TNT-like connections. Western blot analysis suggests that H₂O₂ triggered the phosphorylation of the p38 mitogen-activated protein kinase (MAPK), and that SB203580, a specific inhibitor of p38 MAPK, suppressed the changes in membrane phase properties and cytoskeleton resulting from H₂O₂ treatment. These results suggest that H₂O₂ alters astrocyte membranes and the cytoskeleton through activation of the p38 MAPK pathway.