liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Proteins containing oxidized amino acids induce apoptosis in human monocytes.
Cell Biology Group, Heart Research Institute, Newton, NSW 2042, Australia.
Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Cell Biology Group, Heart Research Institute, Newton, NSW 2042, Australia.
2011 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 435, no 1, 207-216 p.Article in journal (Refereed) Published
Abstract [en]

Cellular deposits of oxidized and aggregated proteins are hallmarks of a variety of age-related disorders, but whether such proteins contribute to pathology is not well understood. We previously reported that oxidized proteins form lipofuscin/ceroid-like bodies with a lysosomal-type distribution and up-regulate the transcription and translation of proteolytic lysosomal enzymes in cultured J774 mouse macrophages. Given the recently identified role of lysosomes in the induction of apoptosis, we have extended our studies to explore a role for oxidized proteins in apoptosis. Oxidized proteins were biosynthetically generated in situ by substituting oxidized analogues for parent amino acids. Apoptosis was measured with Annexin-V/PI (propidium iodide), TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling), MMP (mitochondrial membrane permeabilization), caspase activation and cytochrome c release, and related to lysosomal membrane permeabilization. Synthesized proteins containing the tyrosine oxidation product L-DOPA (L-3,4-dihydroxyphenylalanine) were more potent inducers of apoptosis than proteins containing the phenylalanine oxidation product o-tyrosine. Apoptosis was dependent upon incorporation of oxidized residues, as indicated by complete abrogation in cultures incubated with the non-incorporation control D-DOPA (D-3,4-dihydroxyphenylalanine) or when incorporation was competed out by parent amino acids. The findings of the present study suggest that certain oxidized proteins could play an active role in the progression of age-related disorders by contributing to LMP (lysosomal membrane permeabilization)-initiated apoptosis and may have important implications for the long-term use of L-DOPA as a therapeutic agent in Parkinson's disease.

Place, publisher, year, edition, pages
Portland Press , 2011. Vol. 435, no 1, 207-216 p.
Keyword [en]
aging, apoptosis, DOPA, lysosome, oxidized protein
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-66923DOI: 10.1042/BJ20100682ISI: 000289182100019PubMedID: 21210766OAI: diva2:405293
Available from: 2011-03-22 Created: 2011-03-22 Last updated: 2011-04-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Brunk, Ulf T
By organisation
PharmacologyFaculty of Health Sciences
In the same journal
Biochemical Journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 48 hits
ReferencesLink to record
Permanent link

Direct link