Mechanisms of tubulin modification by phosphatidylcholine hydroperoxides

The interaction of lipid peroxides with cellular proteins has been postulat ed to contribute to cellular aging. A potential target for such effects is tubulin, the building block of microtubules. We examined the concentration- dependent effects of phosphatidylcholine hydroperoxides on the ability of t ubulin to polymerize into microtubules. The results demonstrated that even very low concentrations of peroxides were sufficient to interfere with the tubulin and, therefore, the microtubule function. Decreased tubulin activit y (as measured by tubulin GTPase activity) showed correlation with the modi fication of methionine and cysteine in tubulin and a change in the tubulin conformational state as indicated by fluorescence and ultraviolet spectrosc opic measurements. As no effect on electric conductivity was observed, indi cating that modulation of ionic binding was not involved, the interaction m echanism may be a hydrophobic one.