Extracellular lipid

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

The atherosclerotic plaque consists, on the lumen side, of a layer of connective tissue containing smooth muscle cells and macrophages covering a deeper layer of macrophages containing so much hpid that they are known as foam cells due to their microscopic appearance. This layer also contains a varying amount of cell debris and extracellular lipid. Outside it, there is often a region of proliferated smooth muscle cells. 

Similarly, apolipoprotein E expression increases in neurotoxicity mediated by KA (Table 6.3) (Boschert et al., 1999). Apolipoprotein E is a major lipoprotein in the brain. It is involved in the transport, distribution, and other aspects of cholesterol homeostasis. Apolipoprotein E also plays a dominant role in the mobilization and redistribution of brain lipids in repair, growth, and maintenance of nerve cells (Mahley, 1988). The secretion of apolipoproteins E and D may be differentially regulated in cultured astrocytes. In cell culture systems this depends upon the extracellular lipid milieu (Patel et al., 1995). During neurotoxicity mediated by KA, apolipoprotein E levels increase moderately in astrocytes and apolipoprotein E mRNA increases very strongly in clusters of CA1 and CA3 pyramidal neurons. Based on hybridization in situ and immunohistochemical studies, expression of apolipoprotein E in neurons may be a part of a rescue program to counteract neurodegeneration mediated by KA (Boschert et al., 1999). 

Mauro, T.M. et al., Barrier recovery is impeded at neutral pH, independent of ionic effects implications for extracellular lipid processing, Arch. Dermatol. Res., 290, 215,1998. 

Mammalian stratum comeum (SC) consists of highly comified cells embedded in a matrix of lipid bilayers (Matoltsy, 1976). These extracellular lipids are arranged in the form of multiple lamellae that are believed to constitute the major barrier to percutaneous penetration (Michaels et al., 1975 Elias, 1983). As discussed, the SC lipid membranes are made up predominantly of ceramides, cholesterol, free fatty acids, cholesteryl sulfate, and small amounts of some less well-defined nonpolar components (Gray et al., 1982 Yardley and Summerly, 1981). Six groups of ceramides have been characterized in porcine SC, as shown in Fig. 4 (Wertz et al., 1983). This classification was based on the polarity of the ceramides, with ceramide 1 being the least polar. 

In the past decade a number of physical techniques have been used to evaluate the unique barrier properties of mammalian skin [1]. This chapter deals with the use of another physical technique, fluorescence spectroscopy, to study the barrier properties of the human stratum corneum (SC), specifically with respect to the transport of ions and water. The SC is the outermost layer of the human epidermis and consists of keratinized epithelial cells (comeo-cytes), physically isolated from one another by extracellular lipids arranged in multiple lamellae [2]. Due to a high diffusive resistance, this extracellular SC lipid matrix is believed to form the major barrier to the transport of ions and water through the human skin [3-5]. The objective of the fluorescence studies described here is to understand how such extraordinary barrier properties are achieved. First the phenomenon of fluorescence is described, followed by an evaluation of the use of anthroyloxy fatty acid fluorescent probes to study the physical properties of solvents and phospholipid membranes. Finally, the technique is applied to the SC to study its diffusional barrier to iodide ions and water. 

To understand how the extracellular lipid lamellae act as a barrier to the percutaneous transport of water and ions, detailed information on its structure and accessibility is required. The AF fluorescence membrane probes have been used to provide information on the dynamics of SC membranes. The following sections describe the findings obtained using this approach. 

Extracellular Lipid Signals Glycolipids, Synthesis of Lipidomics... 

The remarkable barrier function of the skin is primarily located in the stratum corneum (SC), the thin, outermost layer of the epidermis. The SC consists of several layers of protein-filled corneocytes (i.e., terminally differentiated keratinocytes) embedded in an extracellular lipid matrix. Attached to the outer cor-neocyte envelope are long-chain covalently bound cer-amides that interact with the lipids of the extracellular space. These lipids are composed primarily of free fatty acids, ceramides, and cholesterol arranged in multiple lamellae.f Passive permeation across the SC is believed to occur primarily via the intercellular... 

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