Biosynthesis and turnover of DOPA-containing proteins by human cells

Kenneth J. Rodgers, Peter M. Hume, Rachael A. Dunlop, Roger T. Dean

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


Protein-bound 3,4-dihydroxyphenylalanine (PB-DOPA) is a major product of hydroxyl radical attack on tyrosine residues of proteins. Levels of PB-DOPA in cells and tissues have been shown to be greatly elevated in age-related diseases. We demonstrate for the first time that l-DOPA (levodopa) can be biosynthetically incorporated into cell proteins by human cells (THP-1 monocytes and monocyte-derived macrophages). The DOPA-containing proteins generated were selectively visualized on PVDF membranes using a redox-cycling staining method. Many cell proteins contained DOPA and seemed to be synthesized as their full-length forms. The cellular removal of DOPA-containing proteins by THP-1 cells was by proteolysis involving both the proteasomal and the lysosomal systems. The rate of cellular proteolysis of DOPA-containing proteins increased at lower levels of DOPA incorporation but decreased at higher levels of DOPA incorporation. The decreased rate of degradation was accompanied by an increase in the activity of cathepsins B and L but the activity of cathepsin S increased only at lower levels of DOPA incorporation. These data raise the possibility that PB-DOPA could be generated in vivo from l-DOPA, which is the most widely used treatment for Parkinson disease.

Original languageEnglish
Pages (from-to)1756-1764
Number of pages9
JournalFree Radical Biology and Medicine
Issue number11
Publication statusPublished - 1 Dec 2004
Externally publishedYes


  • Cathepsin
  • DOPA
  • Free radicals
  • Lysosome
  • Proteasome
  • Protein oxidation


Dive into the research topics of 'Biosynthesis and turnover of DOPA-containing proteins by human cells'. Together they form a unique fingerprint.

Cite this