Nε-(Carboxymethyl)lysine Modification of Elastin Alters Its Biological Properties: Implications for the Accumulation of Abnormal Elastic Fibers in Actinic Elastosis

Abstract

Accumulation of degenerated elastic fibers in the sun-exposed skin designated as actinic elastosis is a histological hallmark of photodamaged skin. Previous studies have indicated that the elastic fibers of actinic elastosis interact with lysozyme and are modified by N(ɛ)-(carboxymethyl)lysine (CML), one of the major advanced glycation end products (AGEs). We studied here how CML modification of elastin is involved in the pathogenesis of actinic elastosis. The CML-modified insoluble elastin became resistant to neutrophil elastase digestion, which was reversed by treatment with aminoguanidine, a potent inhibitor of AGE formation. In a temperature-dependent aggregation assay, CML-modified elastin rapidly formed self-aggregates, the size of which was larger than unmodified elastin. The elastic fiber sheets prepared from CML-modified α-elastin showed 3D wider diameter, tortuous appearance, and decreased elasticity on tensile tests. The CML-modified α-elastin, but not unmodified α-elastin, was found to bind to lysozyme in vitro, supporting the immunohistochemical findings that the antibodies for lysozyme and CML reacted simultaneously with the elastic fibers of actinic elastosis and UV-irradiated skin. The glycated elastin is likely to cause the accumulation of abnormally aggregated elastic fibers and unusual interaction with lysozyme in actinic elastosis.

Beneficial Effects of Lemon Balm Leaf Extract on In Vitro Glycation of Proteins, Arterial Stiffness, and Skin Elasticity in Healthy Adults

“…2). These results support previous findings that the glycation reaction is involved in the formation of fluorescent yellow pigments in lens proteins (16) and the curved fibrous structures in elastin fibers (15). Blood vessels and dermal tissues contain abundant collagen and elastin (31,32).…”

“…The detailed effects of glycation on the structure of elastin and collagen fibers in vivo have not yet been fully clarified; however, degeneration and weakening of glycated artificial elastin fibers in vitro have been reported (15). In addition, increases in yellowish deposits in the glycated protein have been reported (16), suggesting that yellowing skin with aging might be based partly on glycation (17).…”

Protein carbamylation is a hallmark of aging

“…Elastin carbamylation was never suspected before this study. It is known that in vitro glycation is responsible for the alteration of its assembly, proteolytic degradation, or physical properties (46), suggesting that the chemical modifications brought by carbamylation may also impact functional and structural properties of elastin. Herein, it is likely that accumulation of matrix CDPs contributes to skin aging by reducing elasticity and increasing rigidity of skin matrix proteins.…”

Permeation of Hydrophilic Molecules across Glycated Skin Is Differentially Regulated by the Stratum Corneum and Epidermis–Dermis

“…14,15) In addition to the modification of structural proteins, AGEs also induce biological reactions via binding to receptor for AGEs (RAGE).…”

“…13) Moreover, glycation of dermal collagen and elastic fibers contributes to stiffness and loss of elasticity, forming wrinkles. 14,15) In addition to the modification of structural proteins, AGEs also induce biological reactions via binding to receptor for AGEs (RAGE). 16) Binding of AGEs to RAGE induces activation of nuclear factor kappa B (NF-κB) and subsequent transcription of proinflammatory genes including interleukin 1 (IL-1), tumor necrosis factor alpha (TNFα), matrix metalloproteinases (MMPs) and RAGE itself, accelerating further skin aging and deconstruction.…”