Published online before print September 14, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.061064

Accepted for publication August 1, 2007.

Article

Clusterin Associates with Altered Elastic Fibers in Human Photoaged Skin and Prevents Elastin from Ultraviolet-Induced Aggregation in Vitro

Elke Janig^*, Martin Haslbeck, Ariane Aigelsreiter^*, Nathalie Braun, Daniela Unterthor, Peter Wolf, Noor M. Khaskhely^¶, Johannes Buchner, Helmut Denk^*, and Kurt Zatloukal^*@

From the Institute of Pathology* and the Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria; the Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria; the Department of Chemistry, Technical University of Munich, Garching, Germany; and the Department of Immunology,^¶ University of Texas MD Anderson Cancer Center, Houston, Texas

^@ To whom correspondence should be addressed. E-mail: kurt.zatloukal{at}meduni-graz.at.

	Abstract

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 -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.