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Dr Kenneth J Rodgers

The Heart Research Institute
145 Missenden Road, Camperdown, NSW
Email: k.rodgers@hri.org.au
Tel: +61-2-9550-3560
Fax: +61-2-9550-3302
Homepage: http://www.hri.org.au

Proteolysis of oxidised proteins
The progression of various age-related and degenerative diseases is accompanied by an accelerated accumulation of oxidatively damaged proteins in cells and tissues. The key defense against their accumulation is removal by complete proteolysis however this defense is sometimes incomplete as evidenced by their accumulation. To date many observations on oxidised protein catabolism have come from experiments in which cells were exposed to relatively high concentrations of oxidants and are limited by the fact that even moderate doses of oxidants are toxic to cells. To overcome this problem we have developed a new approach in which we supply radiolabelled oxidised amino acids (oxAAs) to cells, and allow them to be incorporated into cellular proteins through protein synthesis. This provides precisely controlled intracellular pools of protein-bound oxAAs.
The biosynthetic approach has allowed us to examine the effects on protein turnover of specific oxAAs such as DOPA a major protein modification found in tissues from age-related pathologies such as cataracts and atherosclerotic plaques. We have also provided evidence that proteasomes and lysosomes are both involved and may possibly operate in tandem in the removal of oxAA-containing proteins. Studies are in progress in which we are using genomic and proteomic approaches to identify the cellular mechanisms involved in the recognition and removal of oxidised and oxAA-containing proteins. Since it is clear that protein oxidation can confer resistance to proteolysis we are interested in examining the role of cross-linking and aggregation in this process and identifying ways in which this resistance to proteolysis can be prevented or reversed in ageing and age-related pathologies.
Prof. Roger T. Dean, University of Canberra.
Dr Nick Dixon, Research School of Chemistry, Australian National University.
Dr Chris Jackson, Bristol Heart Institute, University of Bristol, England.
Dr Michael Davies, Heart Research Institute, Sydney.
Metabolism of Protein-bound DOPA in Mammals. Rodgers K. J. and Dean R. T. The International Journal of Biochemistry and Cell Biology 32: 945-955, 2000

Biosynthetic Incorporation of Oxidised Amino Acids into Proteins and their Cellular Proteolysis. Rodgers K. J., Wang, HJ and Dean, RT. Free Radical Biology and Medicine, 32(8), 766-775, 2002

Recent Developments in the Intracellular Degradation of Oxidised Proteins. Dunlop, R.A. Rodgers K.J. and Dean, RT. Free Radical Biology and Medicine, 33(7), 894-906, 2002

Assessment of Proteasome Activity in Cell Lysates and Tissue Homogenates using Peptide Substrates. Rodgers K.J. and Dean, RT The International Journal of Biochemistry and Cell Biology 35(5), 716-727, 2002

Proleolytic 'Defences' and the Accumulation of Oxidised Polypeptides in Cataractogenesis and Atherogenesis. Dean, RT, Dunlop, RA, Hume, P and Rodgers K.J. Biochem Soc Symp. 2003; (70): 135-46.

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