Biosynthesis and turnover of DOPA-containing proteins by human cells

Rodgers, KJ; Hume, PM; Dunlop, RA; Dean, RT

Biosynthesis and turnover of DOPA-containing proteins by human cells

Rodgers, KJ

Hume, PM Dunlop, RA Dean, RT

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Publication Type:: Journal Article
Citation:: Free Radical Biology and Medicine, 2004, 37 (11), pp. 1756 - 1764
Issue Date:: 2004-12-01

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Field	Value	Language
dc.contributor.author	Rodgers, KJ https://orcid.org/0000-0002-3627-9651	en_US
dc.contributor.author	Hume, PM	en_US
dc.contributor.author	Dunlop, RA	en_US
dc.contributor.author	Dean, RT	en_US
dc.date.available	2004-08-12	en_US
dc.date.issued	2004-12-01	en_US
dc.identifier.citation	Free Radical Biology and Medicine, 2004, 37 (11), pp. 1756 - 1764	en_US
dc.identifier.issn	0891-5849	en_US
dc.identifier.uri	http://hdl.handle.net/10453/14668
dc.description.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. © 2004 Elsevier Inc. All rights reserved.	en_US
dc.relation.ispartof	Free Radical Biology and Medicine	en_US
dc.relation.isbasedon	10.1016/j.freeradbiomed.2004.08.009	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Monocytes	en_US
dc.subject.mesh	Cell Line	en_US
dc.subject.mesh	Lysosomes	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Parkinson Disease	en_US
dc.subject.mesh	Dihydroxyphenylalanine	en_US
dc.subject.mesh	Proteasome Endopeptidase Complex	en_US
dc.subject.mesh	Cathepsins	en_US
dc.subject.mesh	Proteins	en_US
dc.subject.mesh	Protein Biosynthesis	en_US
dc.title	Biosynthesis and turnover of DOPA-containing proteins by human cells	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	37	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
dc.location.activity	ISI:000225366500009	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	37	en_US

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. © 2004 Elsevier Inc. All rights reserved.

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