We have found recently that dendritic spine extension is inhibited through
acrolein conjugation with α- and β-
tubulin proteins during
brain infarction. In this current study, we looked for other
acrolein-conjugated
proteins in the 100,000g precipitate fraction, to clarify how cytoskeleton structure is modified by
acrolein.
Acrolein-conjugated
proteins were sought from
acrolein-treated mouse FM3A and Neuro2a cells and from tissues isolated from mouse
brain infarction. It was found that
vimentin was conjugated with
acrolein, and the conjugated
amino acid residue was Cys328, which is the only Cys residue in
vimentin. It was also found that Cys207, 257, 285, and Lys118 in actin, another cytoskeleton
protein, were conjugated with
acrolein. The structure and localization of
vimentin and actin filaments were changed greatly in
infarct brain in photochemically induced
thrombosis model mice and in
acrolein-treated Neuro2a cells. In addition, degradation of cytoskeleton
proteins was accelerated in the order vimentin > tubulin > actin in mouse
brain infarction. These findings indicate that a dysfunction of the cytoskeleton by
acrolein is strongly involved in the tissue damage during
brain infarction, together with the apoptosis caused by
glyceraldehyde-3-phosphate dehydrogenase and protein degradation by
matrix metalloproteinase-9.