L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro

Sandra W. Chan, Rachael A. Dunlop, Anthony Rowe, Kay L. Double, Kenneth J. Rodgers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Levodopa (l-dopa), a close structural analogue of the protein amino acid l-tyrosine, can substitute for l-tyrosine in protein synthesis and be mistakenly incorporated into newly synthesised proteins in vitro. We show that l- dopa-containing proteins are present in the brain in l-DOPA-treated Parkinson's disease patients and accumulate in specific brain regions. In vitro studies demonstrate that substitution of l-tyrosine residues in proteins with l-DOPA causes protein misfolding and promotes protein aggregation in SH-SY5Y neuroblastoma cells resulting in the appearance of autofluorescent bodies. We show that the presence of l-DOPA-containing proteins causes profound changes in mitochondria and stimulates the formation of autophagic vacuoles in cells. Unlike l-DOPA, which is toxic to cells through its ability to generate radicals, proteins containing incorporated l-DOPA are toxic to SH-SY5Y cells by a mechanism independent of oxidative stress and resistant to antioxidants. These data suggest that the accumulation of l-DOPA-containing proteins in vulnerable cells might negatively impact on cell function.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalExperimental Neurology
Volume238
Issue number1
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Keywords

  • Incorporation
  • L-DOPA
  • L-tyrosine
  • Parkinson's disease
  • Protein

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