Showing papers in "Advances in lipid research in 1991"

Structural and Lipid Biochemical Correlates of the Epidermal Permeability Barrier

Abstract: Publisher Summary This chapter discusses the structural and lipid biochemical correlates of the epidermal permeability barrier. A pivotal point in terrestrial adaptation is prevention of desiccation and maintenance of internal water homeostasis. The outermost integumentary tissue, the epidermis, maintains a reserve of germinal cell layers whose proliferation, stratification, and differentiation result in the production of the outermost layer, the anucleate stratum corneum. The stratum corneum has heterogeneous tissue structure possessing a selected array of enzymatic activity. The sequestration of lipids to intercellular domains and their organization into a unique multilamellar system have broad implications for permeability barrier function, water retention, desquamation, and percutaneous drug delivery. Yet, the functions and organization of specific lipid species in this membrane system are still unknown. Further, elucidation of the molecular architecture and interactions of lipid and nonlipid components of the stratum corneum intercellular domains will be a prerequisite for a comprehensive understanding of stratum corneum function.

The biochemistry and function of stratum corneum lipids.

Abstract: Publisher Summary This chapter discusses the biochemistry and function of stratum corneum lipids. The study of lipids as a class of chemical constituents of the stratum corneum offers a unique opportunity to investigate the functional specialization of this tissue. The daily rate of epidermal lipid synthesis in man is equal to the lipid content times the daily loss of stratum corneum. Total epidermal lipid constitutes approximately 10–14% of the dry weight of mammalian epidermis. However, by themselves, isolated intercellular lipids possess no water-holding capacity. The ability of the intercellular lipids to form lamellar bilayers, in the absence of phospholipids, is dependent upon the amphipathic properties of ceramides, free fatty acids, cholesterol, and perhaps lesser constituents such as cholesterol sulfate and proteolipids. The lamellar bilayers are stabilized in an aqueous environment by van der Waals interactions and hydrogen bonds. Moreover, recently, it has been suggested that a major component of the stratum corneum is a ceramide, consisting of 30 to 34-carbon chain length, N-acyl, ω-hydroxyacids covalently bound to the cornified envelope. This leaflet may serve as a scaffold for the intercellular bilayers, thereby contributing to both the barrier and the cohesive properties of the stratum corneum.

The Regulation and Role of Epidermal Lipid Synthesis

Abstract: One of the key functions of the epidermis is to form a barrier between the organism and the outside world. As shown in Fig. 3, disruptions of the barrier result in a cascade of events that ultimately leads to barrier repair. The initial signal that initiates this repair response is unknown. The exocytosis of preformed lipid-enriched lamellar bodies is the first step in this response, which is followed by an increase in lipid synthesis in the epidermis. Our studies demonstrate that this increase in epidermal lipid synthesis is required for the synthesis of new lamellar bodies and repair of the barrier. Inhibition of epidermal lipid synthesis by artificial membranes or drugs impairs barrier recovery by preventing the reformation of lamellar bodies and the continued secretion of lipid. Whether the stimulation of lipid synthesis is primarily regulated by disturbances in barrier function or secondarily by decreases in the lipid content of the cells due to the utilization of lipid for the formation of lamellar bodies is unknown. Additionally, the precise mechanisms by which lipid synthesis is increased (enzyme activation, transcriptional regulation, etc.) remain to be elucidated. The secretion of lipid-containing lamellar bodies results in the reaccumulation of lipid in the intercellular spaces of the stratum corneum and the recovery of normal barrier function. Epidermal lipid synthesis also is probably required to provide lipid for new cell membrane formation to allow for the increase in epidermal cell proliferation, which is stimulated following barrier disruption. Additionally, epidermal lipid synthesis may provide regulatory molecules or crucial substrates that are required for DNA synthesis. Thus, epidermal lipid synthesis plays a key role in the major biological functions of the epidermis, the cutaneous permeability barrier, and cell proliferation.

Lipids in normal and pathological desquamation.

Abstract: Publisher Summary This chapter presents the evidence that stratum corneum lipids are critical effectors of corneocyte cohesion and desquamation. Lipids in the stratum corneum are in the right place to modulate desquamation; that is, they are localized to the intercellular domain. Because normal desquamation occurs through detachment of single, intact corneocytes, it is reasonable to examine constituents of the cell membrane and intermembrane domain for effectors of this process. Desmosomes are intercellular attachment plaques that appear to function as spot welds in epithelial cell cohesion. A progressive loss of desmosomal structures occurs during stratum corneum transit, such that these structures are fragmentary or absent in the outer layers of normal stratum corneum. Thus, it can be inferred that cohesion of at least these outermost corneocytes normally must be mediated by other factors. A number of hypocholesterolemic agents induce scaling as a prominent side effect. In most instances in which the underlying metabolic defect in genetic disorders of cornification has been defined, inborn errors of lipid metabolism are responsible. Both the drug-induced scaling disorders and the genetic ichthyoses associated with lipid metabolic defects have provided invaluable models for the examination of the role of specific lipids in stratum corneum cohesion/desquamation.

Chemistry and function of mammalian sebaceous lipids.

Abstract: Publisher Summary This chapter discusses the chemistry and function of mammalian sebaceous lipids. Sebaceous glands are small organs of mammalian skin that secrete a lipid mixture, known as sebum, onto the skin surface. Anatomically, sebaceous glands are appendages of the epidermis and share some of its characteristics. For example, both types of tissues are made up of cells that have a short lifetime and have to be constantly replaced, and both are active sites of lipid synthesis. However, the types of lipids made are completely different. The chapter presents a study in which the lipid composition of sebum has been analyzed in detail for about 20 species. Each species produces sebum of a unique composition, although there are often similarities in composition within genera. Intermediates in the biosynthetic pathway to cholesterol, which do not accumulate in other tissues, are fairly common sebum constituents. Even more common are a variety of mono- and diesters, which typically contain unusual fatty acids. The activity of sebaceous glands is under hormonal control. Androgenic hormones cause an increase in gland size by stimulating both the rate of cell division and the rate of lipid accumulation. The increase in androgen levels at puberty causes a large increase in the rate of sebum secretion. In humans, the increase is associated with the appearance of adolescent acne.

Strategies to enhance permeability via stratum corneum lipid pathways.

Abstract: Publisher Summary Stratum corneum (SC) lipids, like those of other biomembranes, can be studied by a variety of biophysical techniques. Methods that have been used to investigate lipid membrane biophysics include X-ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), electron spin resonance (ESR), and infrared (IR) spectroscopy. This chapter discusses the techniques of IR spectroscopy and DSC. These techniques have been particularly useful in establishing the phase behavior of a number of lipid membrane systems. The SC lipid pathway is important to the permeability of water and numerous drugs. Despite differences in lipid composition and distribution, the mechanisms of molecular permeation through the SC and other biomembranes are similar. The technique of Fourier transform IR (FTIR) spectroscopy has been extensively used to study the phase behavior of lipid membranes. The lipids of the SC can also be studied by FTIR techniques.

Lipid metabolism in cultured keratinocytes.

Abstract: Publisher Summary This chapter discusses that cultured keratinocytes provide a suitable model to study epidermal lipid metabolism in relation to keratinocyte differentiation. In this respect, air-exposed cultures are most attractive, because their resemblance to intact epidermal tissue is strong. Moreover, keratinocytes isolated from pathological skin specimens are in many cases able to maintain the morphogenic capabilities of their tissue of origin, and this offers a possibility of comparison with keratinocytes derived from the normal skin. This enables creation of conditions mimicking normal and pathological states in vitro and the possibility to evaluate biological responses at the cellular level. In a study on the effects of pharmacological agents, such as retinoids, glucocorticoids, or various additives of cosmetic preparations, two approaches can be used: (1) various modulators of differentiation can be added to the culture medium before elevating the culture to the air–liquid interface, and their effects on the epidermal differentiation program studied thereafter; and (2) pharmacological agents can be applied topically after completion of differentiation. Their effects on epidermal differentiation, lipid metabolism, and stratum corneum composition and barrier function can be then studied, thus affording an acceptable alternative to experiments with laboratory animals.

Integumental lipids of plants and animals: comparative function and biochemistry.

Abstract: Publisher Summary This chapter provides an overview of the chemical composition, physical structure, and arrangement of integumental lipids. Lipids associated with the integument of organisms consist of a complex mixture of long-chain and cyclic compounds. They can be separated into four major categories: (1) hydrocarbons, (2) oxygenated derivatives of hydrocarbons, (3) cyclic compounds, and (4) polar lipids. The integument can serve an organism in many ways. It provides mechanical protection against injury and serves as a physical barrier to predators and invasion by microorganisms. It regulates the movement of materials, especially water, in and out of the body. In many species, the integument also participates in temperature regulation, respiration, locomotion, chemical and visual communication, and environmental sensing. These and other functions depend upon the unique interaction of specific structural, biochemical, and physiological properties of the integument. In virtually every case, lipids deposited on the surface and/or impregnated within the various layers are a key element.

X-ray diffraction and electron paramagnetic resonance spectroscopy of mammalian stratum corneum lipid domains.

Abstract: Publisher Summary This chapter discusses the application of X-ray diffraction and electron paramagnetic resonance (EPR) spectroscopy to elucidate the structure and organization of the lipid-enriched cellular peripheral domains of the stratum corneum. The two techniques provide confirmatory and complementary information about structure and physical properties on a molecular level. Traditionally, differential scanning calorimetry (DSC) is widely used to obtain information about the heat-induced phase changes in biological membranes, but it must be emphasized that calorimetry does not probe membrane structure. EPR has provided information about the stratum corneum that is both parallel and complementary to information provided by X-ray diffraction. Both techniques provide information on a molecular level about temperature-dependent phase behavior that correlates with DSC determinations. However, X-ray diffraction provides more direct information about structure, whereas EPR provides more direct information about the physical properties of membranes, including polarity, microviscosity, and phase transitions.

Epidermal vitamin D metabolism, function, and regulation.

Abstract: Publisher Summary This chapter presents the autocrine role of vitamin D in the epidermis, that is, production of the hormonally active form of vitamin D in the epidermis, and its modulation of epidermal cell differentiation. The vitamin D endocrine system is important not only in the regulation of calcium homeostasis but also in the growth and differentiation of cells of the immune system and skin. The effect of 1,25-(OH)2 D3 on epidermal cell differentiation may be mediated by the Cai levels of these cells. A better understanding of the basic mechanism of action of 1,25-(OH)2 D3 on the differentiation of keratinocytes may have important pharmacological and therapeutic implications. Manipulation of epidermal 1,25-(OH)2 D3 production could provide a novel approach to the therapy of certain skin diseases characterized by aberrant proliferation and differentiation, such as psoriasis or carcinomas.

Lipid modulators of epidermal proliferation and differentiation.

Abstract: Publisher Summary This chapter describes a diverse group of lipids that have been implicated as effector molecules in various tissues, often including the epidermis. It also presents lipids with more established roles, including platelet-activating factor in cellular inflammation. Moreover, those lipids are also described in the chapter, which are involved with signal transduction processes, such as phosphatidylinositol, phosphatidylcholine, and diacylglycerol. Platelet-activating factor (PAF) is an ether phospholipid with potent physiologic effects. PAF is produced by human dermal fibroblasts as well as by human and murine epidermal cells. Because PAF is known to induce the release and metabolism of arachidonic acid, eicosanoids may mediate some of the activities of PAF. PAF may be released from the same ether-phospholipid precursor for arachidonic acid and its metabolites.