Failure of acute administration with proteasome in

Authors: Naoto Kadoguchi Hiroki Kimoto Ryohei Yano Hiroyuki Kato Tsutomu Araki

Publish Date: 2008/04/19

Volume: 23, Issue: 2, Pages: 147-154

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Abstract

We investigated to determine whether acute administration of proteasome inhibitor can cause dopaminergic cell loss in mice in comparison with that of 1methyl4phenyl1236tetrahydropyridine MPTP The four intraperitoneally administrations of MPTP at 1h intervals to mice decreased significantly the concentration of dopamine 34dihydroxyphenylacetic acid DOPAC and homovanillic acid HVA in the striatum after 5 days in comparison with vehicletreated animals In contrast the three subcutaneously administrations of carbobenzoxyLγtbutylLglutamylLalanylLleucinal PSI did not show significant changes in the concentration of dopamine DOPAC and HVA in the striatum after 5 days in comparison with vehicletreated animals Our Western blot analysis also showed that the four administrations of MPTP at 1h intervals to mice produced a significant reduction of antityrosine hydroxylase antibody TH protein levels in the striatum after 5 days after In PSItreated mice In contrast no significant change of TH protein levels was observed in the striatum 5 days after the final treatment with PSI Furthermore a significant decrease of TH protein levels was observed in the striatum of MPTPtreated mice as compared with PSItreated animals The present study demonstrates that the acute treatment with proteasome inhibitor PSI did not cause the dopaminergic neurotoxicity in mice as compared with acute treatment with MPTP Thus our findings suggest that acute proteasome inhibition is not a reliable model for Parkinson’s disease

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