Irreversible incorporation of L-DOPA into the C-terminus of tubulin as a possible cause of side effects during administration of DOPA to Parkinson patients

BISIG CG; CARBAJAL A; CHESTA ME; ARCE CA

Congreso; XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias.; 2011

L-Dopa can be added to the C-terminus of a-tubulin by tubulin tyrosine ligase, one of the enzymes involved in the postranslational cyclic tyrosination/detyrosination of tubulin. Now, we show that after its incorporation into tubulin present in soluble extracts from rat brain, L-Dopa cannot be released by tubulin carboxypeptidase, the other enzyme participating in the cycle. L-Dopa-tubulin can form microtubules as well as Tyr-tubulin. Amount of Dopa-tubulin in soluble extracts was inferred by analyzing the tyrosination state of tubulin by Western blots revealed with anti- total, Tyr-, Glu- and D2-tubulin. We suggest that during a prolonged administration of L-Dopa to Parkinson patients, L-Dopa-tubulin within cells gradually increases (and other tubulin species decrease), resulting in the formation of microtubules containing L-Dopa-tubulin that affect some of their properties, and this could be in some way responsible for the side effects of prolonged treatment with L-Dopa.