Degradation of HNE-modified proteins--possible role of ubiquitin.
4-Hydroxynonenal (HNE) is a lipid peroxidation product that is able to modify proteins. HNE-modified proteins are degraded to a considerable extend by the proteasomal system. It is unclear whether the recognition of HNE-modified proteins is mediated by ubiquitin, or whether the ubiquitin-independent proteasomal pathway is involved. In this study we demonstrate that HNE-modified GAPDH is preferentially ubiquitinated in vitro. In an attempt to demonstrate the formation of poly-ubiquitinated HNE-modified proteins in living cells we explored E36 fibroblasts. A clear rise in HNE-protein modification could be demonstrated after HNE treatment of the cells. Using inhibitors, we could show that the ubiquitin-dependent, ubiquitin-independent, and the lysosomal pathways affect the presence of HNE-modified proteins. We conclude that, although several proteolytic pathways exist for the degradation of HNE-modified proteins, there is the possibility of involvement of ubiquitin-dependent degradation.
Botzen
Diana
D
Research Institute of Environmental Medicine, Heinrich Heine University, Duesseldorf, Germany.
Grune
Tilman
T
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D025801:Ubiquitin / Q000187:drug effects / Q000378:metabolism*
D000447:Aldehydes; D011506:Proteins; D025801:Ubiquitin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C027576:4-hydroxy-2-nonenal