REGULATION OF PROTEIN L-ISOASPARTYL METHYLTRANSFERASE IN THE HIPPOCAMPUS OF PATIENTS WITH TEMPORAL LOBE EPILEPSY
Abstract number :
2.056
Submission category :
Year :
2002
Submission ID :
3449
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Julie Lanthier, Richard R. Desrosiers, Alain Bouthillier, Marjolaine Lapointe, Michel Demeule, Richard Beliveau. Laboratoire de Medecine Moleculaire, Universite du Quebec a Montreal, Hopital Sainte-Justine, Montreal, Quebec, Canada; Service de Neurochirur
RATIONALE: Protein L-isoaspartyl methyltransferase (PIMT) is implicated in the repair of damaged proteins which have accumulated abnormal aspartyl residues (L-isoaspartyl) during cell aging. Gene targeting has elucidated a physiological role for PIMT by showing that mice lacking PIMT died prematurely from fatal epileptic seizures. Here we investigated the role of PIMT in human epilepsy.
METHODS: We used surgical specimens of hippocampus and neocortex from patients suffering from temporal lobe epilepsy and from control patients to investigate the expression, activity and mRNA of PIMT, as well as the accumulation of proteins damaged by abnormal aspartyl residues in these tissues.
RESULTS: We showed that PIMT activity and expression were 50% lower in epileptic hippocampus than in controls but were unchanged in neocortex. Although the protein was downregulated, PIMT mRNA expression was unchanged in epileptic hippocampus, suggesting post-translational regulation of the PIMT level. Moreover, several proteins with abnormal aspartyl residues accumulate in epileptic hippocampus. Microtubules component tubulin, one of the major PIMT substrates, had an increased amount (2-fold) of L-isoaspartyl residues in the epileptic hippocampus.
CONCLUSIONS: These results demonstrate that the downregulation of PIMT in the hippocampus of patients with temporal lobe epilepsy leads to a significant accumulation of damaged proteins such as tubulin that could contribute to neuron dysfunction in human epilepsy.
[Supported by: The National Sciences and Engineering Research Council of Canada, the Savoie Foundation, the Claude Bertrand Foundation and the FRSQ-FCAR-Sante.]