title: Prolonged oxidative stress on actin.
abstract: Hydrogen peroxide, coming from polymorphonuclear leukocytes, causes severe oxidative injury on actin molecules with the disarrangement of cortical actin cytoskeleton followed by plasmalemma blebbing. In this paper we demonstrate that actin oxidation does not simply develop into denaturation, but oxidative injuries on actin are specific and related to the chemical characteristics of the oxidant. Experiments on purified actin in solution have shown that actin behavior to oxidation depends on (i) the amino acidic targets of the oxidant and (ii) on the structural plasticity of the actin molecule, which differently responds to different chemical modifications. Therefore, hydrogen peroxide (that presents a broad oxidative activity) affects actin dynamics by markedly inhibiting the assembly of actin monomers, by forcing the disassembly of actin polymers, and, moreover, by affecting the interaction between oxidant-stressed actin and DNase I. Diamide (a specific thiol oxidant), in contrast, mainly lowers the actin polymerization extent, while it slightly influences the polymerization rate and results uneffective on both F-actin disassembly and actin-related DNase I inhibition. Actin response to oxidative stresses likely depends on the "structural connectivity in actin," the property allowing it to finely modulate the actin filament architecture. The potential cellular relevance of the alterations in the interaction between oxidized actin and DNase I has been briefly discussed.
authors.affiliation: Laboratory of Biochemistry and Biophysics of Cytoskeletal Structures, University of Milan, Via Celoria 26, Milan, 20133, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Milzani
authors.forename: I
authors.initials: I
authors.lastname: DalleDonne
authors.forename: R
authors.initials: R
authors.lastname: Colombo
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D019281:Dimerization; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018384:Oxidative Stress; D011817:Rabbits
chemical_list: D000199:Actins; D006861:Hydrogen Peroxide