Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Actins / drug effects
-
Actins / metabolism
-
Animals
-
Animals, Newborn
-
Astrocytes / drug effects
-
Astrocytes / metabolism*
-
Brain / metabolism
-
Brain / physiopathology
-
Cell Communication / drug effects
-
Cell Communication / physiology
-
Cell Membrane / drug effects
-
Cell Membrane / metabolism*
-
Cells, Cultured
-
Cytoskeleton / drug effects
-
Cytoskeleton / metabolism*
-
Enzyme Activation / drug effects
-
Enzyme Activation / physiology
-
Enzyme Inhibitors / pharmacology
-
Hydrogen Peroxide / pharmacology*
-
Intercellular Junctions / drug effects
-
Intercellular Junctions / metabolism*
-
Membrane Lipids / metabolism
-
Membranes, Artificial
-
Myosin Heavy Chains / drug effects
-
Myosin Heavy Chains / metabolism
-
Myosin Type V / drug effects
-
Myosin Type V / metabolism
-
Neurodegenerative Diseases / metabolism
-
Neurodegenerative Diseases / physiopathology
-
Oxidants / pharmacology
-
Oxidative Stress / drug effects
-
Oxidative Stress / physiology*
-
Phosphorylation / drug effects
-
Rats
-
p38 Mitogen-Activated Protein Kinases / drug effects
-
p38 Mitogen-Activated Protein Kinases / metabolism
Substances
-
Actins
-
Enzyme Inhibitors
-
Membrane Lipids
-
Membranes, Artificial
-
Myo5a protein, rat
-
Oxidants
-
Hydrogen Peroxide
-
p38 Mitogen-Activated Protein Kinases
-
Myosin Type V
-
Myosin Heavy Chains