Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation

Oba, Chisato; Morifuji, Masashi; Ichikawa, Satomi; Ito, Kyoko; Kawahata, Keiko; Yamaji, Taketo; Asami, Yukio; Itou, Hiroyuki; Sugawara, Tatsuya

doi:10.1371/journal.pone.0136377

Cited by 22 publications

(25 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, dietary milk phospholipids might modulate covalently bound epidermal ceramides associated with the formation of lamellar structures and suppress skin inflammation in hairless mice, resulting in improved skin barrier function (27). In hairless mice, dietary sphingomyelin modulates epidermal structures and prevents disruption of skin barrier function after UVB irradiation (28). Thus, the oral or injectional administration of sphingolipids might have been helpful in improving the skin barrier defects in the present patients.…”

Section: Discussionmentioning

confidence: 96%

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency

Takeichi

Kawamoto

Inoue

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

Neu-Laxova syndrome (NLS) is a term that unifies the independent reports by Neu and Laxova of a lethal multiple congenital anomaly syndrome (1). The main features of NLS involve defective somatic growth and the disturbed development of the central nervous system and skin, as well as many other anomalies that might present primarily as malformations or a malformation sequence (1). In 2014, mutations in PHGDH, which encodes phosphoglycerate dehydrogenase (PHGDH), were found in autosomal recessive cases of NLS (1). In addition, mutations in PSAT1, which encodes phosphoserine aminotransferase 1, and PSPH, which encodes phosphoserine phosphatase, were identified in several autosomal recessive cases of NLS (2). NLS is a genetically heterogeneous disorder that can be caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH (Fig. 1). l-Serine is a nonessential amino acid that is synthesized de novo from the glycolytic intermediate 3-phosphoglycerate through three steps that are respectively catalyzed by PHGDH, phosphoserine aminotransferase, and phosphoserine phosphatase (3). PHGDH deficiency, which is a congenital error of serine metabolism, was first described in 1996, before NLS was proposed as a syndrome (4). PHGDH is the first enzyme in the de novo biosynthesis of serine from carbohydrates. A reduced ability to synthesize l-serine has potentially serious consequences for cellular metabolism (5). Serine is Abstract Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH. l-Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tapestripped stratum corneum of the NLS patient's skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient's stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency.-Takeichi, T.

show abstract

Section: Discussionmentioning

confidence: 96%

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency

Takeichi

Kawamoto

Inoue

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…In bovine milk, phospholipids represent approximately 0.5% to 1% of the total lipid content and mainly consist of sphingomyelin and phosphatidylcholine. Supplemental sphingomyelin (146 mg/kg body weight [BW]/day) significantly suppressed an increase in transepidermal water loss (TEWL) and attenuated a decrease in covalently bound ω‐hydroxy ceramides induced by a single dose of UVB irradiation (20 mJ/cm 2 ) compared with unsupplemented control mice …”

Section: Food Componentsmentioning

confidence: 99%

The beneficial role of functional food components in mitigating ultraviolet‐induced skin damage

Morifuji

2019

Experimental Dermatology

Self Cite

View full text Add to dashboard Cite

Excessive exposure to ultraviolet (UV) radiation can chemically alter biological molecules and is one of the major environmental health risks with potential to damage the structure and function of the skin. Numerous dietary supplements are known to optimize the skin's defenses against radiation exposure. Several studies in which the beneficial roles of functional food components, that can protect against UV‐induced skin damage, have been demonstrated. Supplemental dietary sphingomyelin maintains covalently bound ω‐hydroxy ceramides to avert skin barrier defects after UVB irradiation. The oral administration of collagen hydrolysates has been shown to limit decreases in skin elasticity via increases in the dermal hyaluronic acid content. Milk fermented with lactic acid bacteria has been shown to augment DNA repair mechanisms and improve skin immunity in the aftermath of UVB damage. Furthermore, long‐term ingestion of fermented milk containing lactic acid bacteria, collagen hydrolysates and sphingomyelin increases the minimal erythema dose (MED) in human subjects with moderate sunburn or redness and tanned skin after exposure to UV solar radiation. Thus, products containing these functional food components are one means by which the adverse effects of UV radiation on the skin can be mitigated.

show abstract

“…Bovine milk SM has demonstrated significant potential as an anti-cancer treatment in the colons of mice [22]. In addition, oral consumption of SM in a mouse model demonstrated SM accumulation in the skin and a decreased skin TEWL after UVB [16], [37]. Previous work by De Guzman and Campbell from the Cal Poly Bioimaging Lab suggested bovine milk SM photoprotection for a monolayer of KRTs [13], [14].…”

Section: Bovine Milk Sphingomyelin Past Research and Limitationsmentioning

confidence: 99%

“…The high lipid content in the stratum corneum reduces TEWL, and perturbations of lipid content demonstrate how TEWL is affected. For example, mouse skin damaged by UV light showed an increase in TEWL [37]. In addition, severely burned skin leads to massive dehydration because of increased TEWL [15].…”

Section: Functions Of the Epidermismentioning

confidence: 99%

“…Orally administered bovine milk SM was found to incorporate into the stratum corneum [23]. Additionally, the dietary SM that localized in the skin reduced Transepidermal Water Loss (TEWL) and increased the water content of skin after UVB radiation [37]. Lab research on KRT monolayers by De Guzman and Campbell et al have also demonstrated promising results for SM photoprotection [13], [14].…”

Section: Sphingomyelin As a Natural Alternative To Sunscreenmentioning

confidence: 99%

See 1 more Smart Citation

Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes

Kandell¹

View full text Add to dashboard Cite

Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes Rebecca Marie Kandell Non Melanoma Skin Cancer (NMSC) affects 3.3 million Americans each year and results from Ultra Violet Radiation (UVR) damage to DNA in the form of pyrimidine dimers and photoproducts [1]-[5]. Cells directly detect the damage and initiate apoptosis, cell cycle arrest, or DNA repair by modulating p53 and p21 levels [6]-[9]. Current methods of photoprotection include sunscreen, but controversy over safety of some active ingredients necessitates research into more natural alternatives [10]-[12]. In particular, 24 hour incubation with bovine milk sphingomyelin (BSM) has demonstrated photoprotective potential by reducing p21 and p53 levels in keratinocytes (KRTs) after UV radiation [13], [14]. This thesis aims to expand on past BSM research by exploring the mechanism for photoprotection. Normally, sphingomyelin (SM) is metabolically degraded to ceramide which then leads to cell apoptosis [6]. The goals of this thesis were to characterize a fluorescent SM (FSM) to assess changes in intracellular fluorescence distribution after various incubation and post-UV exposure times. FSM was deemed functionally equivalent to BSM by reducing levels of p21 after UV. Furthermore, quantification demonstrated that FSM trafficking and intracellular fluorescence were independent of continuous incubation time, warranting further investigation into shorter timepoints like 1 hour. Across several post-UV timepoints, the 1 hour incubation had a consistently higher average cytoplasmic mean gray value compared to 24 hour incubation. In addition, the no UV control was significantly lower compared to the 24 hour and 12 hour post-UV timepoints. No post-UV differences were observed for the 24hour incubation, suggesting future work is necessary for the 1 hour incubation, which potentially streamlines future experiments. Two immunofluorescence stains for endogenous SM (lysenin) and ceramide were also optimized for preliminary fluorescence distribution studies and v colocalization with FSM. Finally, a 3T3 fibroblast spheroid model was utilized as proof-ofconcept for future 3D KRT cultures and depth of dye penetration quantification methods. These findings suggest FSM is an appropriate model for BSM trafficking, a shorter FSM incubation time could potentially be adopted in future studies, dual immunofluorescence staining for SM and ceramide is viable, and spheroids provide a promising model for future 3D KRT studies.

show abstract

Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation

Cited by 22 publications

References 45 publications

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency

The beneficial role of functional food components in mitigating ultraviolet‐induced skin damage

Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes

Contact Info

Product

Resources

About