Lipids localization

Flavonoids bear different degrees of hydroxylation, polymerization, and methylation that define both specific and nonspecific interactions with membrane lipids. Molecule size, tridimensional structure, and hydrophili-city/hydrophobicity are chemical parameters that determine the nature and extent of flavonoid interactions with lipid bilayers. The hydrophilic character of certain flavonoids and their oligomers endows these molecules with the ability to bind to the polar headgroups of lipids localized at the water-lipid interface of membranes. On the other hand, flavonoids with hydrophobic character can reach and cross the lipid bilayer. In this section, we will discuss current experimental evidences on the consequences of flavonoid interactions with both the surface and the hydrophobic core of the lipid bilayer. 

Shaw JE, Epand RE, Epand RM, Li Z, Bittman R, Yip CM. Correlated fluorescence-atomic force microscopy of membrane domains structure of fluorescence probes determines lipid localization. Biophys. J. 2006 90 2170-2178. 

These proteins can be modified covalently by lipids —> localizes them to specific membranes. 

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

Protems can be physisorbed or covalently attached to mica. Another method is to innnobilise and orient them by specific binding to receptor-fiinctionalized planar lipid bilayers supported on the mica sheets [15]. These surfaces are then brought into contact in an aqueous electrolyte solution, while the pH and the ionic strength are varied. Corresponding variations in the force-versus-distance curve allow conclusions about protein confomiation and interaction to be drawn [99]. The local electrostatic potential of protein-covered surfaces can hence be detemiined with an accuracy of 5 mV. 

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Baumgartner and coworkers [145,146] study lipid-protein interactions in lipid bilayers. The lipids are modeled as chains of hard spheres with heads tethered to two virtual surfaces, representing the two sides of the bilayer. Within this model, Baumgartner [145] has investigated the influence of membrane curvature on the conformations of a long embedded chain (a protein ). He predicts that the protein spontaneously localizes on the inner side of the membrane, due to the larger fluctuations of lipid density there. Sintes and Baumgartner [146] have calculated the lipid-mediated interactions between cylindrical inclusions ( proteins ). Apart from the... 

The ending caine stems from cocaine, the first clinically employed local anaesthetic. Procaine and tetracaine are ester-linked substances, the others are amides. Amide bonded local anaesthetics usually contain two i s in their name, ester-bonded only one. In the structure drawings, the lipophilic portion of the molecule is depicted at the left, the amine at the right. The asterisk marks the chiral centre of the stereoisomeric drugs. Lipid solubility is given as the logarithm of the water octanol partition coefficient, log(P). 

After local anaesthetic injection, onset of nerve block and duration depends mainly on lipid solubility and on the region in where the diug is injected. In some formulations adrenaline is added to prolong the blocking action by inducing regional vasoconstriction and hereby reduce absorption and metabolisation. 

The amide local anaesthetic lidocaine may also be used as an antianhythmic for ventricular tachycardia and exra-systoles after injection into the blood circulation. Drugs with high lipid solubility such as bupivacaine cannot be used for these purposes because their prolonged binding to the channel may induce dysrhythmias or asystolic heart failure [3]. Systemically applied lidocaine has also been used successfully in some cases of neuropathic pain syndromes [4]. Here, electrical activity in the peripheral nervous system is reduced by used-dependent but incomplete sodium channel blockade. 

SIP is formed from sphingosine by sphingosine kinases (SphKs). Degradation of SIP occurs either reversibly by lipid phosphate phosphohydrolases (LPPs) and SIP phosphatases (SPPs), or irreversibly by SIP lyase (SPL) (Fig. 1). The localization of SIP production is highly important since SIP plays a role both as extracellular mediator and as intracellular... 

HSV2 (herpes simplex virus 2), which causes significant morbidity and is an important cofactor for the transmission of HIV infection was recently targeted in a mouse model by local application of siRNA mixed with lipids. The results suggested that siRNA could work as active components of microbicides to prevent viral infection or transmission [2]. 

A subfamily of Rho proteins, the Rnd family of small GTPases, are always GTP-bound and seem to be regulated by expression and localization rather than by nucleotide exchange and hydrolysis. Many Rho GTPase effectors have been identified, including protein and lipid kinases, phospholipase D and numerous adaptor proteins. One of the best characterized effector of RhoA is Rho kinase, which phosphorylates and inactivates myosin phosphatase thereby RhoA causes activation of actomyosin complexes. Rho proteins are preferred targets of bacterial protein toxins ( bacterial toxins). 

PTKs can be subdivided into two large families, receptor tyrosine kinases (RTKs) and non-RTKs. The human genome encodes for a total of 90 tyrosine kinases of which 32 are nonreceptor PTKs that can be placed in 10 subfamilies (Fig. 1). All nonreceptor PTKs share a common kinase domain and usually contain several additional domains that mediate interactions with protein-binding partners, membrane lipids, or DNA (Table 1). These interactions may affect cellular localization and the activation status of the kinase or attract substrate proteins for phosphorylation reactions. 

The earliest morphological change in the sebaceous follicle is an abnormal follicular epithelial differentiation, which results in ductal hypercornification. Cornified cells in the upper section of the follicular canal become abnormally adherent. Comedones represent the retention of hyperproliferating ductal keratinoc-ytes in the duct. Several factors have been implicated in the induction of hyperproliferation sebaceous lipid composition, androgens, local cytokine production (IL-i, EGF) and bacteria (P. acnes). 

An alternative approach is the use of pH-sensitive fluorophores (Lichtenberg and Barenholz, lOSS). These probes are located at the lipid-water interface and their fluorescence behavior reflects the local surface pH, which is a function of the surface potential at the interface. This indirect approach allows the use of vesicles independent of their particle size. Recently, techniques to measure the C potential of Liposome dispersions on the basis of dynamic light scattering became commercially available (Muller et al., 1986). 

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