Abstract
Proteins are continuously damaged by various intrinsic and extrinsic factors, such as changes in pH and temperature, UV exposure, and oxidative stress loading, which affect intracellular pathways. Most of the damaged proteins are eliminated by protein degradation systems, but some of them are restored by protein repair systems. The formation of L-isoaspartyl (L-isoAsp), D-aspartyl (D-Asp), and D-isoaspartyl residues within proteins, arising from both deamidation of L-asparagine residues and isomerization and/or racemization of L-aspartyl residues, is a frequent chemical modification that alters their conformation and leads to abnormal aggregation. Protein L-isoaspartyl/D-aspartyl O-methyltransferase (PIMT, EC 2.1.1.77) is known as a repair enzyme for L-isoAsp or D-Asp residues in proteins. PIMT is expressed in various tissues such as the brain, liver, heart, and kidney, but its function within the skin is unclear. In this study we demonstrated that the PIMT protein was expressed in human dermal fibroblasts and that the PIMT protein level in fibroblasts was decreased both with aging and by UVB irradiation. Our data indicated that the decrease in PIMT expression level caused an accumulation of L-isoAsp-containing proteins in fibroblasts. Further, UVB irradiation induced isomerization of aspartic acids on its own. These findings suggested that it was important to maintain an adequate PIMT level in the skin. We found that a Birch bark extract and a Wine extract were effective in protecting fibroblasts against the UVB-induced decreases in PIMT protein levels and that the Wine extract was effective even for regeneration. Therefore, “restoring denatured proteins” by PIMT might be a novel and effective approach to anti-aging skin care.
