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21.
Summary The acidic phospholipid phosphatidylserine (PS) has been reported to have variable effects onin vitro hydroxyapatite proliferation. PS promotesin vitro mineralization in systems in which calcium-PS-phosphate complexes are allowed to form, and inhibitsin vitro mineralization when incorporated into liposomes. To investigate these diverse effects, a Langmuir adsorption isotherm was
used to determine the affinity of PS for hydroxyapatite crystals, based on binding of14C-PS to synthetic hydroxyapatite crystals of specific surface 54 m2/g. Using this model, PS was found to bind to hydroxyapatite crystals with an affinity comparable to that of the amino acid
phosphoserine (K=3.33 ml/μmol). Coating the surface of hydroxyapatite seed crystals with PS reduced their rate of proliferation
in a metastable calcium phosphate solution in which calcium-PS-phosphate complexes were previously shown to promote hydroxyapatite
formation. The extent of inhibition of hydroxyapatite seeded growth was directly related to the proportion of the hydroxyapatite
surface covered with PS. These data suggest that PS may have multiple effects on hydroxyapatite formationin situ, and that mineral-PS interactions can retard crystal proliferation. 相似文献
22.
The turtle olfactory epithelium was treated with suspensions of various lipids and their effects on the olfactory responses were examined by measuring the olfactory bulbar responses. The phosphatidylserine (PS)-treatment greatly lowered the threshold for n-valeric acid and enhanced its responses at all concentrations examined. The responses to isovaleric acid and n-butyric acid were also greatly enhanced by the PS-treatment. The responses to ten other odorants examined were a little enhanced or unchanged by the PS-treatment. The enhanced responses to the fatty acids returned to the original level about 10 h after the treatment. It was confirmed that PS was incorporated into olfactory epithelium by incubating the epithelium with PS-suspension containing [14C]PS. The treatment of the epithelium with phosphatidic acid or cardiolipin unchanged or suppressed the responses to odorants including the fatty acids. The present results suggest that lipid aas well as proteins in the receptor membranes play an important role in odor reception. 相似文献
23.
Anthony Collins Donald W. Hilgemann 《Pflügers Archiv : European journal of physiology》1993,423(5-6):347-355
Effects of membrane phospholipids on Na+-Ca2+ exchange and Na+ channel currents were studied in giant excised cardiac sarcolemmal patches. Phospholipids were suspended in an inert vehicle of -tocopherol acetate and hexane and were then directly applied to the side of patch electrodes at a short distance from the tip during current recording. Phosphatidylserine strongly stimulated outward Na+-Ca2+ exchange current and altered the kinetics of cytoplasmic Na+- and Ca2+-dependent secondary modulation. This effect was partially reversed by phosphatidylcholine. Prolonged treatment with phosphatidylserine eliminated the inactivation transient normally observed upon rapid application of cytoplasmic Na+ but left cytoplasmic Ca2+ dependence largely intact. In such cases, subsequent chymotrypsin treatment removed cytoplasmic Ca2+ dependence, but had no further stimulatory effect, indicating maximum alleviation of inactivation by phosphatidylserine. While these results indicate that phosphatidylserine acts on a cytoplasmic, protease-sensitive regulatory domain of the exchanger, phosphatidylserine also stimulated the exchange current after deregulation by chymotrypsin, indicating an effect on the exchange mechanism itself. As in other myocyte preparations, cardiac Na+ currents in giant patches undergo a time-dependent negative shift in the voltage dependence of steady-state inactivation. Loss of phosphatidylserine from the cytoplasmic leaflet (i.e. loss of transbilayer asymmetry of phosphatidylserine distribution) does not appear to be the underlying cause, since phosphatidylserine did not reverse this shift, despite stimulation of Na+-Ca2+ exchange current in the same patches. 相似文献
24.
Efferocytosis as an apoptotic cell (AC) clearance mechanism facilitates the removal of dangerous and damaged cells, an important process in regulating normal homeostasis. Failure to correctly execute apoptosis and efferocytosis is associated with atherosclerosis, as well as chronic inflammatory and autoimmune disorders such as systemic lupus erythematosus (SLE). Effective and timely efferocytosis involves various molecules that act as “Find-Me” signals or as alarmins to quickly allow identification by phagocytic cells. In recent years, most of these molecules have been investigated, but less attention has been paid to the nuclear molecules associated with efferocytosis of ACs and necrotic cells (NCs). These molecules have several functions including acting as alarmin signals for faster recognition of ACs, facilitating the cleanup of ACs and for maintaining self-tolerance. The same group of molecules is also implicated in several inflammatory and autoimmune diseases. Previous studies have shown that these molecules also serve as targets for pharmacological agents such as necrostatins, recombinant Fcnb, anti-histone, neutralizing antibodies, calbiochem, aminophylline, activated protein C, CD24IgG recombinant fission protein, and recombinant thrombomodulin. Thus, greater understanding of these molecules/pathways will enable developments in the treatment and/or prevention of various disorders, especially autoimmune diseases. Here, we review current knowledge about the mechanisms by which nucleic acids, histones, nucleosomes and monosodium urate microcrystals (MSU) can act as alarmins/“Find-Me” signals, how they might be stimulated in defective efferocytosis and their function and importance as biomarkers for prognosis and treatment of atherosclerosis, inflammatory disorders and autoimmune diseases. 相似文献
25.
The behavioral effects of 5 days of administration of phosphatidylserine (PS) was studied in aged rats. The intraperitoneal (5, 10, and 20 mg/kg) or intracerebroventricular (5, 10, and 20 μg/2 μl) injection of PS liposomes caused a facilitated acquisition of active avoidance behavior as studied in shuttle-box and pole jumping test situations. The retention of active and passive avoidance responses was also improved. No substantial difference between PS-treated and control animals was apparent either in the responsiveness to electrical footshock or in the motor activity tested in an open field. Grooming behavior appeared to be enhanced in rats treated with the highest dose of the substance. Since PS affects both central catecholaminergic and cholinergic transmission, which is known to be impaired in old animals, the possibility that the behavioral effects of PS involve brain dopamine and/or acetylcholine systems is discussed. 相似文献
26.
Lang F Lang PA Lang KS Brand V Tanneur V Duranton C Wieder T Huber SM 《Pflügers Archiv : European journal of physiology》2004,448(3):319-324
Infection of erythrocytes by the malaria pathogen Plasmodium falciparum leads to activation of several distinct anion channels and a non-selective, Ca2+-permeable cation channel. All channel types are presumably activated by the oxidative stress generated by the pathogen. Similar or identical channels are activated by oxidation of non-infected erythrocytes. Activation of the non-selective cation channel allows entry of Ca2+ and Na+, both of which are required for intracellular growth of the pathogen. The entry of Ca2+ stimulates an intraerythrocytic scramblase that facilitates bi-directional phospholipid migration across the bilayer, resulting in breakdown of the phosphatidylserine asymmetry of the cell membrane. The exposure of phosphatidylserine at the outer surface of the cell membrane is presumably followed by binding to phosphatidylserine receptors on macrophages and subsequent phagocytosis of the affected erythrocyte. The lysosomal degradation may eventually eliminate the pathogen. The channel may thus play a dual role in pathogen survival. Absence of the channels is not compatible with pathogen growth, enhanced channel activity accelerates erythrocyte apoptosis that may represent a host defence mechanism serving to eliminate infected erythrocytes. 相似文献
27.
目的研究脓毒症患者外周血红细胞的形态改变及红细胞膜表面磷脂酰丝氨酸(PS)的外露情况。方法采用配对设计随机分组方法,分别对正常对照组(n=30)和脓毒症患者组(n=30)进行静脉采血,行瑞氏染色血涂片观察和测定红细胞聚集指数,并采用对Ps有高度亲和力的磷脂结合蛋白AnnexinV检测技术,利用流式细胞仪对红细胞进行荧光测定。结果显微镜下观察脓毒症患者外周血红细胞形态发生明显异常改变,呈棘形、泪滴形、球形、缗线形等变化,细胞明显聚集;同时红细胞聚集指数测定结果显示脓毒症组较正常对照组也明显升高,其差异有统计学意义(P〈0.05)。脓毒症组Ps外露的红细胞比例明显高于正常对照组,其差异有统计学意义(P〈0.001)。结论脓毒症患者外周血红细胞表面Ps的外露表达明显增加,同时红细胞形态发生明显异常变化。 相似文献
28.
Zhong-yi Hu Grace Y. Sun Philip G. Rhodes 《Alcoholism, clinical and experimental research》1992,16(3):432-435
Phosphatidylserine is enriched in the brain and has been implicated to play a role in regulating neuronal membrane functions. In this study, three experimental protocols were used to examine the effects of in utero ethanol exposure on phosphatidylserine biosynthesis in rat pup brain, namely, (1) assay of the serine base-exchange enzyme activity in brain microsomes, (2) incubation of brain slices with [3H] serine, and (3) incorporation in vivo of [3H]serine into phosphatidylserine as well as serine-related phospholipids in brain. Results from all three protocols point to a decrease in phosphatidylserine biosynthesis in newborn rat pup cerebrum on exposure to ethanol in utero compared with the pair-fed controls. When in utero ethanol-exposed pups were nursed by mothers given a chow diet, the differences gradually returned to control levels by 17 days of age. The decrease in phosphatidylserine biosynthesis may be important in explaining some of the neuronal deficits associated with in utero ethanol exposure. 相似文献
29.
Spectrin has been shown to interact with phosphatidylserine (PS), however, the precise binding sites for PS in spectrin have not been defined. In the present study, we have identified specific PS binding sites in spectrin using recombinant spectrin fragments encompassing the entire sequences of both spectrin chains. We show that sites of high affinity are located within eight of the 38 triple-helical structural repeats which make up the bulk of both chains: these are: α8 and α9-10, and β2, β3, β4, β12, β13 and β14, and PS affinity was also found in the non-homologous N-terminal domain of the β-chain. It is noteworthy that the PS-binding sites in β-spectrin are clustered in close proximity to the sites of attachment both of ankyrin and of 4.1R, the proteins engaged in attachment of spectrin to the membrane. We conjecture that direct interaction of spectrin with PS in the membrane complements modulates its interactions with the proteins, and that (considering also the known affinity of 4.1R for PS) the formation of PS-rich lipid domains, which have been observed in the red cell membrane, may be a result. 相似文献
30.
Chlorhexidine (CHX) is an antibacterial agent used in various types of pharmaceutical products. Therefore, CHX is easily found around us. Owing to its positive charge, the electrochemical property of cell membranes was assumed to be a key point of cytotoxic action of CHX. Depolarization of membranes attenuated the cytotoxic action of CHX in rat thymic lymphocytes. CHX interfered with annexin V binding to membranes. Manipulations to induce exposure of phosphatidylserine on the outer membrane surface augmented the cytotoxic action of CHX, indicating that changes in the electrochemical property of membranes affected the cytotoxic action of CHX. Hence, CHX might kill cells physiologically undergoing apoptosis, resulting instead in necrotic cell death. However, the threshold CHX concentration in this in vitro study was slightly higher than blood CHX concentrations observed clinically. Therefore, these results may support the safety of CHX use although CHX possesses unique cytotoxic actions described in this study. 相似文献