Activation of SIRT1 Enhances Epidermal Permeability Barrier Formation through Ceramide Synthase 2– and 3–Dependent Mechanisms

Shin, Kyong‐Oh; Lim, Chaehun; Park, Hye Yoon; Kim, Sungeun; Kim, Bogyeong; Lee, Yerin; Chung, Hwa-Jee; Jeong, Sekyoo; Park, Keedon; Park, Kyungho

doi:10.1016/j.jid.2019.12.021

Cited by 13 publications

(13 citation statements)

References 20 publications

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“…Skin surface lipids collected by D-Squame tape were analyzed using LC/MS/MS, and significant reduction of squalene was only observed in test product-treated site (Figure5A), which was consistent with the in vitro sebosuppressive activity of test peptide. Recently, we reported that SIRT1 activation peptide treatment stimulated the epidermal keratinocyte differentiation through ceramide synthase 2-and 3-mediated signaling 20. Higher resemblance in structural and biological properties of test peptide to those of previously reported one20 suggests similar differentiation promoting activity of test peptide in skin.…”

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confidence: 70%

“…Recently, we reported that SIRT1 activation peptide treatment stimulated the epidermal keratinocyte differentiation through ceramide synthase 2-and 3-mediated signaling 20. Higher resemblance in structural and biological properties of test peptide to those of previously reported one20 suggests similar differentiation promoting activity of test peptide in skin. As a marker lipid for epidermal lipids constituting stratum corneum intercellular lamellar structure for skin barrier function, significant increase in cholesterol concentration was observed in test product-treated site after 8 weeks of usage (Figure5B).…”

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confidence: 70%

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Topical application of autophagy‐activating peptide improved skin barrier function and reduced acne symptoms in acne‐prone skin

Lee

Shin

et al. 2020

J of Cosmetic Dermatology

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Background: Recent studies about the important roles of autophagy signaling in sebaceous lipogenesis and epidermal differentiation suggest potential benefits of autophagy activation in acne. Aims: To investigate the effects of an autophagy activator on acne-prone skin. Methods: Autophagy signaling in human immortalized SZ95 sebocytes, normal human epidermal keratinocytes, and 3D reconstituted skin was examined. Effects of an autophagy-activating peptide on sebaceous lipogenesis were measured by fluorescence microscopic analysis. The clinical efficacy in acne-prone skin was evaluated through an eight-week, double-blind, randomized, vehicle-controlled study. Changes in skin surface lipid compositions were further analyzed. Results: In cultured sebocytes and keratinocytes, the investigated autophagy-activating peptide increased LC3-II expression, indicating a stimulation of autophagy signaling. Testosterone and linoleic acid treatment induced lipogenesis in cultured sebocytes and is further inhibited by the autophagy activator peptide treatment. How to cite this article: Lee Y, Shin K, Shin K-O, et al. Topical application of autophagy-activating peptide improved skin barrier function and reduced acne symptoms in acne-prone skin.

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confidence: 70%

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confidence: 70%

Topical application of autophagy‐activating peptide improved skin barrier function and reduced acne symptoms in acne‐prone skin

Lee

Shin

et al. 2020

J of Cosmetic Dermatology

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“…Because prior studies demonstrated that ceramides containing long-chain fatty acids (FAs) with 22–26 carbons in length are generated by CerS2 and CerS3 during de novo synthesis [ 13 ], we further determined the carbon chain lengths of FA of ceramides which were enhanced by PS. Consistent with prior findings [ 14 ], we showed that treatment with IL-4 significantly reduces the contents of ceramides with 22–26 carbon-containing FAs in cells ( Figure 4 A–E).…”

Section: Resultsmentioning

confidence: 99%

“…Ceramides, a class of sphingolipids containing a backbone of a sphingoid base (or referred to as sphingosine) that is linked to a fatty acid (FA) via an amide bond, are the predominant lipid comprising approximately 50% of the SC lipid content by mass, and the most effective structural component for the formation of the epidermal permeability barrier [ 12 ]. Ceramides are produced in the skin through two major pathways [ 13 ]: (i) the de novo synthesis pathway that is initiated by serine palmitoyltransferase (SPT) and catalyzes the condensation of serine and palmitoyl-CoA to produce 3-ketosphiganine, which is further metabolized to sphinganine. Sphinganine is then amide-linked (N-acylated) by ceramide synthases (CerSs) to generate ceramides with different acyl chain lengths; and (ii) the sphingomyelinase (SMase)-dependent hydrolysis of sphingomyelin, a key component of the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

N-Palmitoyl Serinol Stimulates Ceramide Production through a CB1-Dependent Mechanism in In Vitro Model of Skin Inflammation

Shin

Kim

Park³

et al. 2021

IJMS

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Ceramides, a class of sphingolipids containing a backbone of sphingoid base, are the most important and effective structural component for the formation of the epidermal permeability barrier. While ceramides comprise approximately 50% of the epidermal lipid content by mass, the content is substantially decreased in certain inflammatory skin diseases, such as atopic dermatitis (AD), causing improper barrier function. It is widely accepted that the endocannabinoid system (ECS) can modulate a number of biological responses in the central nerve system, prior studies revealed that activation of endocannabinoid receptor CB1, a key component of ECS, triggers the generation of ceramides that mediate neuronal cell fate. However, as the impact of ECS on the production of epidermal ceramide has not been studied, we here investigated whether the ECS stimulates the generation of epidermal ceramides in an IL-4-treated in vitro model of skin inflammation using N-palmitoyl serinol (PS), an analog of the endocannabinoid N-palmitoyl ethanolamine. Accordingly, an IL-4-mediated decrease in cellular ceramide levels was significantly stimulated in human epidermal keratinocytes (KC) following PS treatment through both de novo ceramide synthesis- and sphingomyelin hydrolysis-pathways. Importantly, PS selectively increases ceramides with long-chain fatty acids (FAs) (C22–C24), which mainly account for the formation of the epidermal barrier, through activation of ceramide synthase (CerS) 2 and Cer3 in IL-4-mediated inflamed KC. Furthermore, blockade of cannabinoid receptor CB1 activation by AM-251 failed to stimulate the production of total ceramide as well as long-chain ceramides in response to PS. These studies demonstrate that an analog of endocannabinoid, PS, stimulates the generation of specific ceramide species as well as the total amount of ceramides via the endocannabinoid receptor CB1-dependent mechanism, thereby resulting in the enhancement of epidermal permeability barrier function.

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“…Murine SC samples were collected by stripping off the D-Squame tape applied onto the back of the mice. SC samples were harvested from these D-Squame tapes and lysed in radioimmunoprecipitation assay buffer, and next, sphingolipids were extracted as per the procedures we have described previously [ 70 , 71 ]. The extracted lipids were dried in a vacuum system (Vision, Seoul, Republic of Korea), re-dissolved in methanol, and analyzed by liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS; API 3200 QTRAP mass; AB/Sciex, Framingham, MA, USA) in the selective ion monitoring mode.…”

Section: Methodsmentioning

confidence: 99%

Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin

Kim

Lee

et al. 2021

IJMS

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Inactive cortisone is converted into active cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11β-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11β-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11β-HSD1 knockout mice (n = 11), 11β-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11β-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11β-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.

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Activation of SIRT1 Enhances Epidermal Permeability Barrier Formation through Ceramide Synthase 2– and 3–Dependent Mechanisms

Cited by 13 publications

References 20 publications

Topical application of autophagy‐activating peptide improved skin barrier function and reduced acne symptoms in acne‐prone skin

Topical application of autophagy‐activating peptide improved skin barrier function and reduced acne symptoms in acne‐prone skin

N-Palmitoyl Serinol Stimulates Ceramide Production through a CB1-Dependent Mechanism in In Vitro Model of Skin Inflammation

Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin

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