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Oxidized proteins: Intracellular distribution and recognition by the proteasome

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Abstract

The formation of oxidized proteins is one of the highlights of oxidative stress. In order not to accumulate such proteins have to be degraded. The major proteolytic system responsible for the removal of oxidized proteins is the proteasome. The proteasome is distributed throughout the cytosolic and nuclear compartment of mammalian cells, with high concentrations in the nucleus. On the other hand a major part of protein oxidation is taking place in the cytosol. The present review highlights the current knowledge on the intracellular distribution of oxidized proteins and put it into contrast with the concentration and distribution of the proteasome.

Section snippets

Protein oxidation and distribution of oxidized proteins

Proteins are attacked by various oxidants and as the consequence a variety of amino acids is modified [8], [9], [10]. Besides the side chain modification also a cleavage of the polypeptide backbone might occur, resulting in the formation of smaller fragments [8], [9], [10]. Regardless of the large variety of amino acid derivatives formed under in vitro conditions in cellular systems the variety of protein oxidation products is even larger, since a secondary protein modification by oxidation

The proteasomal system and the distribution of its components

To maintain the cellular function and integrity it is required to have systems available that are able to recognize and degrade damaged or misfolded proteins in a fast and efficient way, in order to prevent their aggregation and cross-linking, e.g. the formation of lipofuscin [44], [45], [46]. Such an aggregate is insoluble, non-degradable and perhaps lethal for a cell from a certain degree of accumulation [46]. To prevent such accumulation of protein aggregates several protein-degrading

Intracellular localization of the degradation of oxidized proteins

Comparing the investigated distributions of damaged proteins after various oxidative stresses and the proteasomal distribution, it seems likely, that the cell is able to keep the nuclear protein pool free of damage, while the cytosolic proteins are accumulating oxidative markers. Whether this is the result of a limited protein oxidation in the nucleus, a very efficient degradation of the damaged nuclear proteins, due to the high proteasome content, or whether there are systems involved

Acknowledgments

The work of TG was supported by BMU, DFG SFB 575, DFG GK1033 and the Heinrich Heine University Research Foundation.

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