Mechanisms of tubulin modification by phosphatidylcholine hydroperoxides.

The interaction of lipid peroxides with cellular proteins has been postulated 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 tubulin 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 activity (as measured by tubulin GTPase activity) showed correlation with the modification of methionine and cysteine in tubulin and a change in the tubulin conformational state as indicated by fluorescence and ultraviolet spectroscopic measurements. As no effect on electric conductivity was observed, indicating that modulation of ionic binding was not involved, the interaction mechanism may be a hydrophobic one.