Inhibition of colchicine binding to rat liver tubulin by aldehydes and by linoleic acid hydroperoxide.
The onset of fat accumulation within CCl4 poisoned hepatocytes, occurring as early as 1 h after treatment, is known to be provoked by a block in lipoprotein secretion. Lipoprotein secretion involves the function of the microtubular system. Several data indicate that this early block in lipoprotein secretion is not primarily the consequence of impaired protein synthesis. Therefore effects of some derivatives of lipid peroxidation, i.e. aldehydes and linoleic acid hydroperoxide were investigated. The results described in this paper shown that the above mentioned lipid peroxidation derivatives inhibit, with different activities, [3H] colchicine binding to liver high-speed supernates. Percentage binding inhibition is directly related to concentrations of aldehydes of LAHPO. LAHPO is more effective than aldehydes. Among the aldehydes tested, 4-hydroxypentenal, produced during lipid peroxidation of biological materials, was the most active. The presence of thiols, added to the incubation medium, partially protects against the inhibition of [3H] colchicine binding by aldehydes. This suggests that aldehydes act by reacting with -SH groups of tubulin. The possibility that interaction between lipoperoxidation derivatives and tubulin in vivo may contribute to the onset of fat infiltration in CCl4 poisoning is discussed.
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D003078:Colchicine / Q000378:metabolism*; D003864:Depression, Chemical; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D008041:Linoleic Acids / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D000447:Aldehydes; D006023:Glycoproteins; D008041:Linoleic Acids; D014404:Tubulin; D003078:Colchicine