Skin - ‘That Unfakeable Young Surface'

Guy, Richard H.

doi:10.1159/000351939

Cited by 6 publications

(5 citation statements)

References 51 publications

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“…SC superstructure can be described with a brick and mortar model, where (im)permeable bricks represent corneocytes (dead cells), surrounded by a mortar which represents a lipid matrix made of ceramides, fatty acids, and cholesterol . Most compounds have been shown to penetrate by the intercellular pathway, i.e., through the lipid matrix . The presence of ceramides and fatty acids with long saturated chains and cholesterol predispose the SC lipids to occur in the gel phase under physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

Rationalization of Reduced Penetration of Drugs through Ceramide Gel Phase Membrane

et al. 2014

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Since computing resources have advanced enough to allow routine molecular simulation studies of drug molecules interacting with biologically relevant membranes, a considerable amount of work has been carried out with fluid phospholipid systems. However, there is very little work in the literature on drug interactions with gel phase lipids. This poses a significant limitation for understanding permeation through the stratum corneum where the primary pathway is expected to be through a highly ordered lipid matrix. To address this point, we analyzed the interactions of p-aminobenzoic acid (PABA) and its ethyl (benzocaine) and butyl (butamben) esters with two membrane bilayers, which differ in their fluidity at ambient conditions. We considered a dioleoylphosphatidylcholine (DOPC) bilayer in a fluid state and a ceramide 2 (CER2, ceramide NS) bilayer in a gel phase. We carried out unbiased (100 ns long) and biased z-constraint molecular dynamics simulations and calculated the free energy profiles of all molecules along the bilayer normal. The free energy profiles converged significantly slower for the gel phase. While the compounds have comparable affinities for both membranes, they exhibit penetration barriers almost 3 times higher in the gel phase CER2 bilayer. This elevated barrier and slower diffusion in the CER2 bilayer, which are caused by the high ordering of CER2 lipid chains, explain the low permeability of the gel phase membranes. We also compared the free energy profiles from MD simulations with those obtained from COSMOmic. This method provided the same trends in behavior for the guest molecules in both bilayers; however, the penetration barriers calculated by COSMOmic did not differ between membranes. In conclusion, we show how membrane fluid properties affect the interaction of drug-like molecules with membranes.

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Section: Introductionmentioning

confidence: 99%

Rationalization of Reduced Penetration of Drugs through Ceramide Gel Phase Membrane

et al. 2014

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“…Kanda and Watanabe [19 ]demonstrated that estradiol suppresses apoptosis in keratinocytes by promoting Bcl-2 expression and induces the expression of cyclin D2, an important cell-cycle regulatory protein [20]. Estrogen may also play a role in the stratum corneum barrier function [21,22,23,24]. …”

Section: Discussionmentioning

confidence: 99%

Intrinsic versus Extrinsic Aging: A Histopathological, Morphometric and Immunohistochemical Study of Estrogen Receptor β and Androgen Receptor

Seleit¹,

Bakry²,

Repey

et al. 2016

Skin Pharmacol Physiol

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Skin is a target organ of sex steroids which play important roles in skin health and disease. The aim of this study is to investigate the expression of estrogen receptor β (ERβ) and androgen receptor (AR) in human skin from different age groups for a better understanding of the hormonal regulation of skin aging. Using standard immunohistochemical techniques, biopsies of sun-unprotected and sun-protected skin were taken from 60 normal subjects. Sun-protected skin showed significantly higher immunoreactivity for ERβ and AR compared to sun-unprotected skin of all age groups. Significantly higher ERβ H score and percent of expression were associated with the 20-35 years age group compared to the groups that were 35-50 years and >50 years old (p < 0.02, p = 0.03, respectively) in sun-unprotected and sun-protected skin (p < 0.001, p = 0.01, respectively). AR H score showed a negative correlation with age (p = 0.04) with no significant difference in immunoreactivity in different age groups, either in sun-unprotected or sun-protected skin. There was also a significant correlation between ERβ H score and epidermal thickness in sun-unprotected (p = 0.04) and sun-protected skin (p = 0.04) in studied subjects regardless of age. The same relationships did not reach significance with AR expression. However, a significant positive correlation was detected between H scores and percent of expression of ERβ and AR in sun-unprotected (p = 0.01, p = 0.02, respectively) and sun-protected skin (p = 0.005, p = 0.02, respectively) regardless of age. In conclusion, both ERβ and AR decline gradually with intrinsic and extrinsic aging. This decline is more obvious with extrinsic aging. Further large-scaled studies are recommended to expand, validate and translate current findings to clinically significant, diagnostic and therapeutic applications. Molecular studies to investigate the probable ligand-independent action of both receptors are warranted. In addition, their gene expression patterns and associated signaling and metabolic pathways can also be tackled to provide a basis for further interventions in pathological processes that involve their dysregulation.

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“…20 Peter Elias' 'brick and mortar' concept of the barrier has been widely accepted and studied in detail using various physical-chemicalstructural and experimental approaches, each contributing to a better understanding of the barrier function. [21][22][23][24][25] As more studies have emerged, it has become clear that the establishment and maintenance of a healthy skin barrier relies on coordinated processes from keratinocyte proliferation to desquamation that must constantly adapt to the environmental conditions (for indepth reviews, please consult "Skin barrier", Elias & Feingold, Eds., 2005). 26 The initially ignored epidermal tight junctions (TJ) and their structural remnants that persist in the SC were shown…”

Section: New Players In the Epidermal Barrier Functionmentioning

confidence: 99%