Acetaldehyde substoichiometrically inhibits bovine neurotubulin polymerization.

Abstract

Acetaldehyde is known to form covalent adducts with tubulin and to inhibit microtubule formation. Available evidence indicates that lysine residues are prominently involved in adduct formation. Previous work has shown that lysines on tubulin can be divided into two general classes based upon their reactivity toward acetaldehyde; those of normal reactivity ("bulk" lysines) and a highly reactive lysine (HRL) located on the a-polypeptide subunit. We took advantage of the fact that the HRL is unreactive when tubulin is in the microtubule form to differentiate the effects of bulk from HRL adducts on tubulin polymerization. Under conditions where both bulk lysines and HRL formed adducts, 0.2 mol acetaldehyde/mol tubulin caused complete inhibition of polymerization. When we modified bulk lysines, but not HRL, tubulin polymerized essentially normally. Finally, when we first blocked bulk lysines on microtubules (HRL unreactive) using unlabeled acetaldehyde and then measured the amount of ["4Clacetaldehyde adduct formed with tubulin after depolymerization (HRL reactive), 0.08 mol acetaldehyde/mol tubulin resulted in completely impaired polymerization. These data show that microtubule formation is very sensitive to even small mole fractions of acetaldehydemodified tubulin (especially with HRL) and further suggest that small amounts of acetaldehyde adduct could be damaging to cytoskeleton function in the cell.

Multilevel regulation of autophagosome content by ethanol oxidation in HepG2 cells

“…Acetaldehyde binds to a highly reactive lysine residue on the α tubulin subunit, thereby slowing its association with the tubulin β subunit and their subsequent polymerization into microtubules. 19 The latter comprise the principal cellular transit system by which AVs fuse with lysosomes for subsequent AV degradation. Our findings suggest that acetaldehyde generation via ADH initiated this process and its action was augmented by reactive species derived from enhanced CYP2E1 catalysis.…”

Ethanol Induces Fatty Acid Synthesis Pathways by Activation of Sterol Regulatory Element-binding Protein (SREBP)

“…Furthermore, the effect of ethanol appeared to be somewhat selective, because SREBP-1 but not SREBP-2 levels were increased in the cells and the mouse livers. An additional explanation could be the formation of acetaldehyde adducts with mature SREBP-1 and, subsequently, inhibition of SREBP-1 degradation, because acetaldehyde is known to form adducts with a number of proteins (36,42,43).…”

Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption.

“…Previous in vitro studies have demonstrated the formation of acetaldehyde adducts with several hepatic proteins and cell constituents (2)(3)(4)(5)(6)(7)(8). Acetaldehyde derived from oxidation of ['4C]ethanol by rat liver slices has also been shown to bind to preformed hepatocyte proteins (28).…”