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

• Published in: The Journal of biological chemistry Vol. 282; no. 32; pp. 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: Journal Article
• Language: English
• Published: United States 10.08.2007
• 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
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M701586200

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.