PMID- 15528035
OWN - NLM
STAT- MEDLINE
DCOM- 20050418
LR  - 20221017
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 37
IP  - 11
DP  - 2004 Dec 1
TI  - Biosynthesis and turnover of DOPA-containing proteins by human cells.
PG  - 1756-64
AB  - 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.
FAU - Rodgers, Kenneth J
AU  - Rodgers KJ
AD  - Cell Biology Unit, The Heart Research Institute, Camperdown, Sydney, NSW 2050, 
      Australia. k.rodgers@hri.org.au
FAU - Hume, Peter M
AU  - Hume PM
FAU - Dunlop, Rachael A
AU  - Dunlop RA
FAU - Dean, Roger T
AU  - Dean RT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Proteins)
RN  - 63-84-3 (Dihydroxyphenylalanine)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Cathepsins/metabolism/physiology
MH  - Cell Line
MH  - Dihydroxyphenylalanine/analysis/*metabolism
MH  - Humans
MH  - Lysosomes/physiology
MH  - Macrophages/chemistry/*metabolism
MH  - Monocytes/chemistry/*metabolism
MH  - Parkinson Disease/metabolism
MH  - Proteasome Endopeptidase Complex/physiology
MH  - Protein Biosynthesis
MH  - Proteins/chemistry/*metabolism
EDAT- 2004/11/06 09:00
MHDA- 2005/04/19 09:00
CRDT- 2004/11/06 09:00
PHST- 2004/03/31 00:00 [received]
PHST- 2004/07/06 00:00 [revised]
PHST- 2004/08/12 00:00 [accepted]
PHST- 2004/11/06 09:00 [pubmed]
PHST- 2005/04/19 09:00 [medline]
PHST- 2004/11/06 09:00 [entrez]
AID - S0891-5849(04)00643-4 [pii]
AID - 10.1016/j.freeradbiomed.2004.08.009 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2004 Dec 1;37(11):1756-64. doi: 
      10.1016/j.freeradbiomed.2004.08.009.