Structural change and degradation of cytoskeleton due to the acrolein conjugation with vimentin and actin during brain infarction

Abstract

We have found recently that dendritic spine extension is inhibited through acrolein conjugation with αand 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. Acroleinconjugated 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.

Deep resequencing of the 1q22 locus in non-lobar intracerebral hemorrhage

“…38 This preventive pathway occurs at the expense of reactive oxygen species (ROS) production, as well as of other potential toxic metabolic byproducts, such as acrolein, 39 a highly reactive compound reported to be more toxic than common ROS. 40 Cytotoxic and neurotoxic effects of acrolein have been extensively reported, and high acrolein levels have been proposed to mediate pathological mechanisms underlying brain infarction in mouse models, [41][42][43] as well as blood vessel rupture in cellular models. [44][45][46][47] Elevated levels of acrolein and SSAT have also been detected in the plasma of stroke patients and have been proposed as candidate stroke biomarkers.…”

Deep Resequencing of the 1q22 Locus in Non‐Lobar Intracerebral Hemorrhage

“…36 This preventive pathway occurs at the expense of reactive oxygen species production, as well as of other potential toxic metabolic byproducts, such as acrolein, 37 a highly reactive compound reported to be more toxic than common reactive oxygen species. 38 Cytotoxic and neurotoxic effects of acrolein have been extensively reported, and high acrolein levels have been proposed to mediate pathological mechanisms underlying brain infarction in mouse models, [39][40][41] as well as blood vessel rupture in cellular models. [42][43][44][45] Elevated levels of acrolein and SSAT have also been detected in the plasma of stroke patients, and have been proposed as candidate stroke biomarkers.…”

Polyamine Homeostasis in Development and Disease

“…In addition to brain infarction, acrolein also causes tissue damage during dementia, renal failure, and in primary Sjogren's syndrome, possibly through conjugation and modulation of key proteins. Mechanistically, recent studies have shown that acrolein conjugation with tubulins inhibits dendritic spine extension [103], and that acrolein conjugation with vimentin and actin alters the structure of the cytoskeleton following brain infarction [104]. Importantly, levels of protein-conjugated acrolein are a biomarker for risk and severity of these diseases [105].…”