Clusterin associates with altered elastic fibers in human photoaged skin and prevents elastin from ultraviolet-induced aggregation in vitro.
Clusterin is a secreted glycoprotein with stress-induced expression in various diseased and aged tissues. It shares basic features with small heat shock proteins because it may stabilize proteins in a folding-competent state. Besides its presence in all human body fluids, clusterin associates with altered extracellular matrix proteins, such as beta-amyloid in Alzheimer senile plaques in the brain. Because dermal connective tissue alterations occur because of aging and UV radiation, we explored the occurrence of clusterin in young, aged, and sun-exposed human skin. Immunohistochemical analysis showed that clusterin is constantly associated with altered elastic fibers in aged human skin. Elastotic material of sun-damaged skin (solar elastosis), in particular, revealed a strong staining for clusterin. Because of the striking co-localization of clusterin with abnormal elastic material, we investigated the interaction of clusterin with elastin in vitro. A chaperone assay was established in which elastin was denatured by UV irradiation in the absence or presence of clusterin. This assay demonstrated that clusterin exerted a chaperone-like activity and effectively inhibited UV-induced aggregation of elastin. The interaction of both proteins was further analyzed by electron microscopy, size exclusion chromatography, and mass spectrometry, in which clusterin was found in a stable complex with elastin after UV exposure.
Janig
Elke
E
Institute of Pathology, Medical University of Graz, Graz, Austria.
Haslbeck
Martin
M
Aigelsreiter
Ariane
A
Braun
Nathalie
N
Unterthor
Daniela
D
Wolf
Peter
P
Khaskhely
Noor M
NM
Buchner
Johannes
J
Denk
Helmut
H
Zatloukal
Kurt
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051152:Clusterin / Q000502:physiology*; D004547:Elastic Tissue / Q000528:radiation effects* / Q000648:ultrastructure; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008875:Middle Aged; D011485:Protein Binding; D012867:Skin / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D015595:Skin Aging / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
C495242:CLU protein, human; D051152:Clusterin; D004549:Elastin