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 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.
Kueper
Thomas
T
Department of Biochemistry and Molecular Biology, Hamburg University, 20146 Hamburg, Germany. thomas_kueper@arcor.de
Grune
Tilman
T
Prahl
Stefanie
S
Lenz
Holger
H
Welge
Vivienne
V
Biernoth
Tanja
T
Vogt
Yvonne
Y
Muhr
Gesa-Meike
GM
Gaemlich
Astrid
A
Jung
Tobias
T
Boemke
Gerrit
G
Elsässer
Hans-Peter
HP
Wittern
Klaus-Peter
KP
Wenck
Horst
H
Stäb
Franz
F
Blatt
Thomas
T
D000595:Amino Acid Sequence; D002469:Cell Separation; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism*; D015595:Skin Aging; D014746:Vimentin / Q000737:chemistry* / Q000502:physiology*
D014746:Vimentin