Biosynthesis and turnover of DOPA-containing proteins by human cells

Kenneth Rodgers, Peter Hume, Rachael Dunlop, Roger Dean

    Research output: Contribution to journalArticlepeer-review

    36 Citations (Scopus)

    Abstract

    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 Medicine
    Volume37
    Issue number11
    DOIs
    Publication statusPublished - 2004

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

    Cite this