The impact of carbonylated proteins on the skin and potential agents to block their effects

Abstract

Carbonylated proteins (CPs) are synthesized by reactions between amino groups in proteins and reactive aldehyde compounds (RAC) yielded from lipid peroxidation initiated by reactive oxygen species (ROS). In the skin, CPs are detected in a higher frequency at sun‐exposed sites of the skin in elderly subjects. Since CPs in the stratum corneum (SC) have been reported to correlate with skin water content and transepidermal water loss, it is considered that the accumulation of CPs in the SC involves the loss of skin moisture functions. However, the roles of CPs in the dermis on skin physiology are still unclear. The purpose of this study was to investigate the roles of CPs in the dermis during the progression of photoaged skin and to propose a method to prevent or reduce the synthesis of CPs. The exposure of human normal dermal fibroblasts to CPs increased intracellular ROS levels and the synthesis of intracellular CPs. In addition, CPs caused morphological changes of fibroblasts. Furthermore, CPs caused alterations of mRNA expression levels of dermal matrix‐related proteins, such as upregulating MMP‐1 and IL‐8. These results indicated that CPs disrupt construction of the dermal matrix. On the other hand, α‐tocopherol and β‐carotene suppressed the synthesis of RAC during lipid peroxidation which resulted in the reduction of UVA‐induced CPs in the SC. From these results, we propose that extracellular CPs increase intracellular ROS levels and contribute to alterations of the dermal matrix. To prevent the synthesis of CPs, the application of α‐tocopherol or β‐carotene could be effective.

Xanthophyll Carotenoids Reduce the Dysfunction of Dermal Fibroblasts to Reconstruct the Dermal Matrix Damaged by Carbonylated Proteins

“…On the other hand, the synthesis of CPs, which are also termed lipid-peroxidation end-products, is initiated by aldehyde compounds yielded by lipid peroxidation by ROS 21 . In a previous study, we found that CP-BSA elevates intracellular levels of ROS in fibroblasts, and results in the accumulation of CPs in fibroblasts 6 . The process of CP accumulation is considered to result in the generation of aldehyde compounds such as acrolein.…”

“…The cellular functions of fibroblasts can be modulated by surrounding CPs and may cause some problems in the metabolism of the dermal matrix. In fact, our previous study suggested the possibility that CP-BSA, which is a model of extracellular soluble CPs, promotes the degradation of dermal matrix proteins by MMP-1 and IL-8/ CXCL8 that are upregulated at the mRNA expression level 6 . MMP-1 is a critical enzyme that cleaves fibrillar type I collagen, and IL-8/CXCL8 is an important chemokine that recruits neutrophils that produce elastase in the dermis 10 13 .…”

“…These facts suggest that scavenging acrolein would be an effective approach to reduce extracellular CPs in addition to reducing ROS. In our previous study, we reported that carotenoids including β-carotene scavenged acrolein 6 . These facts suggest that carotenoids would suppress the dysfunction of fibroblasts induced by extracellular soluble CPs on regeneration of the dermal matrix.…”

“…CPs, one type of oxidized proteins, are synthesized by reactions between reactive aldehyde compounds RACs yielded during lipid peroxidation and the amino groups of lysine and arginine residues in proteins. Because CPs have a yellow brown color, the shift in skin color to yellow-dark with aging has been explained as the accumulation of CPs dermal matrix 6 . Extracellular soluble CPs increase intracellular CP levels though the generation of reactive oxygen species ROS , and concomitantly alter cell shape to be enlarged and flattened.…”

An <i>Ocimum basilicum</i> Extract Containing Rosmarinic Acid Restores the Disruption of Collagen Fibers Caused by Repetitive UVA Irradiation of Dermal Fibroblasts

“…Thus, CPs are regarded as a footprint of higher oxidation levels. Furthermore, our recent study reported that CPs enhance the biosynthesis of MMP-1 through the elevation of intracellular ROS 10 . These facts indicate the importance of reducing levels of ROS in order to ameliorate the deleterious changes of collagen mediated by UVA.…”