P-80 - Effects of oxidants and electrophiles on vimentin assembly

Abstract

The intermediate filament protein vimentin constitutes a critical sensor for electrophiles and oxidative stress in mesenchymal cells. The structure of the vimentin network structure is altered by lipoxidation, although the mechanisms involved are not completely understood. Here, we have studied the response of vimentin to oxidation and lipoxidation, both in vitro and in cells. Electrophilic lipids including 15d-PGJ2 and HNE bind to isolated vimentin in vitro, whereas the oxidant diamide induces disulfide bond formation. Requirement for the presence of the cysteine residue differs among these modifications. Interestingly, pre-incubation of vimentin with these agents disrupts NaCl-induced filament formation, whereas NaCl polymerized-vimentin appears to be more resistant to filament disruption by electrophiles and oxidants. These observations suggest that (lip)oxidative modifications of soluble vimentin subunits would be more deleterious than modification of polymerized vimentin. Therefore, we are exploring the interplay between vimentin lipoxidation and dynamics in cells. These studies will contribute to understand the implications of vimentin in pathophysiological processes associated with oxidative stress.