Vimentin is the specific target in skin glycation. Structural prerequisites, functional consequences, and role in skin aging

Until now, the glycation reaction was considered to be a nonspecific reaction between reducing sugars and amino groups of random proteins. We were able to identify the intermediate filament vimentin as the major target for the AGE modification N(epsilon)-(carboxymethyl)lysine (CML) in primary human...

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Published in:The Journal of biological chemistry 2007-08, Vol.282 (32), p.23427-23436
Main Authors: Kueper, Thomas, Grune, Tilman, Prahl, Stefanie, Lenz, Holger, Welge, Vivienne, Biernoth, Tanja, Vogt, Yvonne, Muhr, Gesa-Meike, Gaemlich, Astrid, Jung, Tobias, Boemke, Gerrit, Elsässer, Hans-Peter, Wittern, Klaus-Peter, Wenck, Horst, Stäb, Franz, Blatt, Thomas
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Cell Separation
Electrophoresis, Gel, Two-Dimensional
Fibroblasts - metabolism
Glycosylation
Humans
Immunohistochemistry
Mass Spectrometry
Molecular Sequence Data
Protein Binding
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Skin - metabolism
Skin Aging
Vimentin - chemistry
Vimentin - physiology
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Summary:Until now, the glycation reaction was considered to be a nonspecific reaction between reducing sugars and amino groups of random proteins. We were able to identify the intermediate filament vimentin as the major target for the AGE modification N(epsilon)-(carboxymethyl)lysine (CML) in primary human fibroblasts. This glycation of vimentin is neither based on a slow turnover of this protein nor on an extremely high intracellular expression level, but remarkably it is based on structural properties of this protein. Glycation of vimentin was predominantly detected at lysine residues located at the linker regions using nanoLC-ESI-MS/MS. This modification results in a rigorous redistribution of vimentin into a perinuclear aggregate, which is accompanied by the loss of contractile capacity of human skin fibroblasts. CML-induced rearrangement of vimentin was identified as an aggresome. This is the first evidence that CML-vimentin represents a damaged protein inside the aggresome, linking the glycation reaction directly to aggresome formation. Strikingly, we were able to prove that the accumulation of modified vimentin can be found in skin fibroblasts of elderly donors in vivo, bringing AGE modifications in human tissues such as skin into strong relationship with loss of organ contractile functions.
ISSN:0021-9258
DOI:10.1074/jbc.M701586200