Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar bodies and stratum corneum barrier lipid organization

Menon, Gopinathan K.; Orsó, Evelyn; Aslanidis, Charalampos; Crumrine, Debra; Schmitz, Gerd; Elias, Peter M.

doi:10.1007/s00403-014-1478-2

Cited by 9 publications

(6 citation statements)

References 33 publications

(32 reference statements)

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“…Moreover, mutations in ceramide synthase 3 have also been shown to be a cause of autosomal recessive congenital ichthyosis that leads to a specific loss of ceramides with very long acyl chains from C26‐C34 . In Refsum disease, the SC intercorneocyte space has also been reported to be non‐uniform with some areas having appropriate lamellar structures and others that completely lacked them . In many cases, a complete absence of corneocyte lipid envelopes was also observed.…”

Section: Variations In Sc Ceramide Levelsmentioning

confidence: 99%

The chemistry, function and (patho)physiology of stratum corneum barrier ceramides

Moore¹,

Rawlings²

2017

Intern J of Cosmetic Sci

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Research on understanding of the chemistry, function and (patho)-physiology of stratum corneum (SC) lipids and especially ceramides has evolved over the last two decades. This has been made successful through the application of separation techniques that have become increasingly more sophisticated, and it has become increasingly evident that our understanding of these molecules remains in its infancy. Thirteen classes of ceramides with over 300 and possibly up to 1000 distinct ceramide species have been identified suggesting an exquisitely subtle relationship between the types of ceramides and physical and chemical behaviour. Nevertheless, research has demonstrated the importance of the correct SC lipid lamellar architecture with conformationally-ordered lipid bilayers, the presence of long-chain ceramides, as either free or covalently bound lipids, greater quantities of phytosphingosine-containing ceramides and a high SC lipid/protein ratio is essential for optimal barrier function. These features are known to change in a variety of physiological and pathophysiological conditions. Clearly, there is more to be learned but as we further decipher the complexity of SC lipids and understand their individual roles in the SC, we will learn how to better treat the disorders of cornification.R esum e Des recherches sur la compr ehension de la chimie, de la fonction et de la (patho)physiologie des lipides du stratum corneum (SC) et en particulier des c eramides ont evolu e au cours des deux derni eres d ecennies. Cela a et e couronn e de succ es grâce a l'application de techniques de s eparation qui sont devenues de plus en plus sophistiqu ees et il est devenu de plus en plus evident que notre compr ehension de ces mol ecules reste a ses d ebuts. Treize classes de c eramides avec plus de 300 et eventuellement jusqu' a 1000 esp eces distinctes de c eramide ont et e identifi ees, ce qui sugg ere une relation tr es subtile entre les types de c eramides et le comportement physicochimique. N eanmoins, la recherche a d emontr e l'importance de l'exactitude de l'architecture lamellaire lipidique du SC avec la conformation en bicouches lipidiques, de la pr esence de c eramides a longue chaîne, qu'ils soient libres ou li es de fac ßon covalante, de la plus grandes quantit es de c eramides contenant de la phytosphingosine et un taux elev e de lipides / prot eines du SC, est essentiel pour une fonction de barri ere optimale. Ces caract eristiques sont connues pour varier suivant les conditions physiologiques et pathophysiologiques. De toute evidence, il y a plus a apprendre, mais a mesure que nous d echiffrions davantage la complexit e des lipides du SC et que nous comprenons leurs rôles individuels dans le SC, nous apprendrons a mieux traiter les troubles de la k eratinisation.

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Section: Variations In Sc Ceramide Levelsmentioning

confidence: 99%

The chemistry, function and (patho)physiology of stratum corneum barrier ceramides

Moore¹,

Rawlings²

2017

Intern J of Cosmetic Sci

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“…In Refsum disease, accumulation of phytanic acid, a metabolites of phytol lead to central nervous system pathologies, and also ichthyosis and skin barrier dysfunction [23]. While earlier ultrastructural observations on Refsum disease focused on general ichthyotic features of epidermis as well as lipid droplets in the basal layers, information on the epidermal LBs-the basis of the permeability barrier as well as orderly desquamation-was lacking.…”

Section: Refsum Diseasementioning

confidence: 99%

“…Experimental studies on barrier disruption followed by metabolic interventions highlighted the role of these organelles in repair and restoration of the barrier following its disruption, as well as control of its formation and secretion by various cytokines and ionic signals within the epidermis [17]. A plethora of studies on gene knockout mice models as well as human skin diseases have added valuable information on developmental pathways and genes critical for the control of LB synthesis, secretion and post-secretory processing of its contents that govern not only the permeability barrier, but also proper desquamation, skin health and disease mechanisms [18][19][20][21][22][23]. Proteomic approaches have identified over 900 different proteins that are expressed within the LB population [24].…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

An overview of epidermal lamellar bodies: Novel roles in biological adaptations and secondary barriers

Menon

Lee

2018

Journal of Dermatological Science

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The epidermal lamellar bodies (LBs) are specialized organelles that contain pro-barrier lipids imparting a fully lamellar internal structure, but also other cargoes such as enzymes (lipid metabolizing and proteolytic), enzyme inhibitors, and antimicrobial peptides. Thus, the LB secretory system, by virtue of delivering these cargoes to the stratum corneum (SC) interstices, is essential for forming the various skin barriers located in the SC. Ultrastructural studies have suggested that the morphologic features of LBs reflect the functional status of the SC. Several ichthyotic skin diseases as well as experimental animal models with defective epidermal lipogenesis show only partial lamellar contents or even empty appearing LB, reflecting an abnormal cargo composition. We suggest that LB polymorphism reflects a wide array of barrier adaptations to environmental challenges, rather than just a defective barrier function, based on observations on a) LB morphology in inherited skin disorders of lipid metabolism (Refsum disease, Chanarin-Dorfman syndrome) characterized by deficiency of lamellar lipids and accumulation of toxic metabolites; b) Psoriasis (with a high expression of Psoriasin antimicrobial peptide within lesions) and c) the Pitohui, a toxic bird where diet-derived toxin is eliminated via the LB secretory system that creates a chemical defense system. Morphological features of LBs from these models suggest a hitherto unrecognized function for the LBs in elimination of toxic substances from the body. We also provide preliminary evidence that indicate yet another function for the LBs- as a type of recycling endosomes allowing for uptake of certain topically applied materials by the epidermis.

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“…The symptoms of this disorder progress with life and include progressive retinitis pigmentosa and hearing loss, anosmia, polyneuropathy, cardiac arrhythmias, unsteadiness of gait, and ichthyosis ( 125 ). The symptom affecting the skin becomes apparent relatively late in life, as late as adolescence or even at the age of 30 or 40 years ( 126 ). The accumulation of PA in human skin causes an abnormal shape of lamellar bodies, which may cause a change in the organization of lipid lamellae ( 127 ).…”

Section: Introductionmentioning

confidence: 99%

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

Zwara

Wertheim–Tysarowska²,

Mika

2021

Front. Med.

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The skin is a flexible organ that forms a barrier between the environment and the body's interior; it is involved in the immune response, in protection and regulation, and is a dynamic environment in which skin lipids play an important role in maintaining homeostasis. The different layers of the skin differ in both the composition and amount of lipids. The epidermis displays the best characteristics in this respect. The main lipids in this layer are cholesterol, fatty acids (FAs) and ceramides. FAs can occur in free form and as components of complex molecules. The most poorly characterized FAs are very long-chain fatty acids (VLCFAs) and ultra long-chain fatty acids (ULCFAs). VLCFAs and ULCFAs are among the main components of ceramides and are part of the free fatty acid (FFA) fraction. They are most abundant in the brain, liver, kidneys, and skin. VLCFAs and ULCFAs are responsible for the rigidity and impermeability of membranes, forming the mechanically and chemically strong outer layer of cell membranes. Any changes in the composition and length of the carbon chains of FAs result in a change in their melting point and therefore a change in membrane permeability. One of the factors causing a decrease in the amount of VLCFAs and ULCFAs is an improper diet. Another much more important factor is mutations in the genes which code proteins involved in the metabolism of VLCFAs and ULCFAs—regarding their elongation, their attachment to ceramides and their transformation. These mutations have their clinical consequences in the form of inborn errors in metabolism and neurodegenerative disorders, among others. Some of them are accompanied by skin symptoms such as ichthyosis and ichthyosiform erythroderma. In the following review, the structure of the skin is briefly characterized and the most important lipid components of the skin are presented. The focus is also on providing an overview of selected proteins involved in the metabolism of VLCFAs and ULCFAs in the skin.

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Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar bodies and stratum corneum barrier lipid organization

Cited by 9 publications

References 33 publications

The chemistry, function and (patho)physiology of stratum corneum barrier ceramides

The chemistry, function and (patho)physiology of stratum corneum barrier ceramides

An overview of epidermal lamellar bodies: Novel roles in biological adaptations and secondary barriers

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

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