Effects of fatty acid sucrose esters on ceftibuten transport by rat intestinal brush-border membrane vesicles

The effects of fatty acid sucrose esters on membrane lipid dynamics and ceftibuten transport by rat intestinal brush-border membrane vesicles (BBMV) were examined to clarify the differences in the action of mono- and poly-acyl sucrose esters on the drug transport. Fatty acid sucrose mono-acyl ester (SS) inhibited ceftibuten transport by BBMV similar to the action of polyoxyethylene sorbitans (Tweens), while fatty acid sucrose polyacyl ester mixtures (F-160 and F-140) did not affect the drug transport by BBMV. SS but not F-160 and F-140 caused an increase in the anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH)- and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene iodide (TMA-DPH)-labeled BBMV in a concentration-dependent manner. Thus, the uptake of ceftibuten by BBMV was strongly correlated with the lipid fluidity of BBMV, in the outer layer and in the inner hydrophobic regions; however, there was no strong correlation between the membrane lipid fluidity and the drug uptake by BBMV. The micelle size and the size distribution of F-160 and F-140 were larger and more widely dispersed, respectively, compared to those of SS and Tweens. These results suggest that the effects of fatty acid sucrose esters on ceftibuten transport by BBMV are related to the dispersion parameter of these pharmaceutical adjuvants.     

Retrospect of a pharmacologist''s life]

Two fluorescent probes were used for the measurement of membrane fluidity in patients on haemodialysis and continuous ambulatory peritoneal dialysis. 1,6-Diphenyl-1,3,5-hexatriene (DPH) anisotropy gives an indication of lipid order and pyrene measures lateral diffusion through the membrane. Pyrene dimer/monomer ratio was significantly lower than controls in both pre-dialysis and post-dialysis samples but DPH anisotropy was unchanged. Both methods showed an increase in membrane fluidity across a 4 hour haemodialysis session. There was an increase in membrane fluidity in CAPD patient samples which was more marked using DPH than pyrene. These results suggest that the two probes give different but complementary information about changes in membrane fluidity and may be more informative when used together rather than singly.     

Acute fracture of the ulna occurring in a professional pitcher

AIM: To study the protective effects of tetrandrine (Tet) on CCl4-injured hepatocytes. METHODS: The cultured rat liver cells were poisoned by CCl4 (10 mmol.L-1). The membrane fluidity was detected by 1,6-diphenyl-1,3,5-hexatriene (DPH), a lipid probe. The Ca2+ concentration was assayed with Fura 2-AM, a sensitive calcium indicator. RESULTS: Tet (1-1000 nmol.L-1) increased viability of liver cell (from 71% to 72%-89%), reduced lactate dehydrogenase (LDH) release, and malondialdehyde (MDA) formation. Tet prevented the heightening of the intracellular Ca2+ concentration and the attenuation of the membrane fluidity of liver cells (P < 0.05). CONCLUSION: Tet had a protective effect on CCl4-injured hepatocytes by inhibiting the lipid peroxidation, improving the membrane fluidity, and lessening the Ca2+ concentration.     

Membrane fluidity increases during apoptosis of sheep ileal Peyer's patch B cells

To investigate specific plasma membrane structural changes associated with apoptosis, whole cells and purified plasma membranes of apoptotic B cells from the ileal Peyer's patch of sheep were analyzed for their "membrane fluidity." The ileal Peyer's patch of sheep provided a large number of B cells required for plasma membrane isolation (> 5 x 10(9)). As the incidence of apoptosis increased with time of culture, the fluidity of purified plasma membranes, as measured with the fluorophore DPH (diphenylhexatriene), increased. To evaluate this phenomenon with intact cells, B cells at different apoptotic stages were fractionated on discontinuous Percoll gradients. Similar results were obtained using the fluorophore TMA-DPH (trimethylammoniumdiphenylhexatriene), which has been shown to localize specifically to the plasma membrane. Functionally, the increase in plasma membrane fluidity associated with apoptosis may represent either a mechanism to cycle phosphatidylserine to the outer leaflet, mediating phagocytic recognition of apoptotic cells, or a consequence of this event.     

In vitro effect of GF120918, a novel reversal agent of multidrug resistance, on acute leukemia and multiple myeloma cells

Resistance to chemotherapy in multiple myeloma (MM) and acute myeloid leukemia (AML) is frequently caused by multiple drug resistance (MDR), characterized by a decreased intracellular drug accumulation. MDR is associated with expression of P-glycoprotein (P-gp). GF120918, an acridine derivative, enhances doxorubicin cell kill in resistant cell lines. In this study, the effect of GF120918 on MDR cell lines and fresh human leukemia and myeloma cells was investigated. The reduced net intracellular rhodamine-123 (Rh-123) accumulation in the MDR cell lines RPMI 8226/Dox1, /Dox4, /Dox6 and /Dox40 as compared with wild-type 8226/S was reversed by GF120918 (0.5-1.0 microM), and complete inhibition of rhodamine efflux was achieved at 1-2 microM. This effect could be maintained in drug-free medium for at least 5 h. GF120918 reversal activity was significantly reduced with a maximum of 70% in cells incubated with up to 100% serum. GF120918 significantly augmented Rh-123 accumulation in vitro in CD34-positive acute leukemia (AML) blasts and CD38-positive myeloma (MM) plasma cells obtained from 11/27 de novo AML and 2/12 refractory MM patients. A significant correlation was observed between a high P-gp expression and GF120918 induced Rh-123 reversal (P=0.0001). Using a MRK16/IgG2a ratio > or = 1.1, samples could be identified with a high probability of GF120918 reversal of Rh-123 accumulation. In conclusion, GF120918 is a promising MDR reversal agent which is active at clinically achievable serum concentrations.     

Extender components and surfactants affect boar sperm function and membrane behavior during cryopreservation

To determine how the individual components of extenders affected boar sperm function and membrane structure and to test a new surfactant's cryoprotective ability, boar sperm were cryopreserved in straws in BF5 extender plus or minus egg yolk plus or minus glycerol plus or minus a surfactant (Orvus ES Paste [OEP] or various concentrations of Pluronic F-127). After thawing, sperm function and fluidity of the isolated head plasma membrane (HPM) were determined. Total motility and adenosine triphosphate content (a measure of viability) were superior postthaw in sperm extended in egg yolk plus glycerol (P < 0.05); neither surfactant improved function. Egg yolk plus any other ingredients improved normal acrosome morphology, whereas a combined measure of motility and normal acrosome morphology was better in the presence of 0.33% OEP or 0.1% Pluronic F-127 (P < 0.05 vs. controls). Head plasma membrane was isolated from freshly collected spermatozoa and spermatozoa cryopreserved in the various extenders. Membrane fluidity was monitored with the probes cis-parinaric acid (cPNA), transparinaric acid (tPNA), and 1,6-diphenyl-1 ,3,5-hexatriene (DPH). The cPNA and the DPH monitor the fluidity of gel and liquid-crystalline areas of the membrane, whereas the tPNA preferentially monitors the gel-phase domains of the membrane. Additionally, DPH monitors the hydrophobic core of the bilayer. In the HPM from fresh sperm, the fluidity of each domain changed over time in a manner unique to that domain, and the behavior of the DPH domain varied among boars. The fluidity dynamics of each domain responded uniquely to cryopreservation. The cPNA domain was unaffected, the tPNA domain was altered by four of the eight extenders, and all extenders affected the fluidity of the DPH domain. Membrane structure was significantly correlated with cell function for sperm cryopreserved in extenders that preserved viability and motility. Sperm cryopreserved in egg yolk plus glycerol plus either OEP or 0.1% Pluronic F-127 functioned best when the bulk domains were less fluid initially and the gel domain solidified more slowly. Therefore, the behavior of domains in the HPM of boar spermatozoa is affected by cryopreservation and is related to the postthaw function of boar sperm cryopreserved in different extenders.     

Simultaneous determination of benzene, toluene, ethylbenzene, and xylenes in urine by thermal desorption-gas chromatography

Amphotericin B (AmB)-resistant Leishmania donovani promastigotes were selected by increasing drug pressure, and their biological features were compared with those of the wild-type parent strain. The 50% inhibitory concentration for resistant cells was 20 times higher than that for the wild-type. Resistance was stable after more than 40 passages in drug-free medium, and resistant promastigotes were infective to macrophages in vitro but lost their virulence in vivo. They had 2.5 times longer generation time, decreased AmB uptake, and increased AmB efflux in comparison to the wild type. Fluorescence measurement with a specific plasma membrane probe, 1-[4-(trimethylammonio)-1,6-diphenylhexa]-1,3,5-triene, showed increased membrane fluidity in drug-resistant promastigotes. Analysis of lipid composition showed that in resistant cells saturated fatty acids were prevalent, with stearic acid as the major fatty acid, and the major sterol was an ergosterol precursor, the cholesta-5, 7, 24-trien-3beta-ol and not ergosterol as in the AmB-sensitive strain.     

Fluorescence anisotropy--a parameter for characterizing membrane fluidity

The lipophilic fluorescent probe diphenylhexatriene (DPH) has been shown previously to behave as a marker of plasma membrane in living cell systems, and it is therefore been widely used in membrane fluidity studies via fluorescence anisotropy measurements. The anisotropic coefficient, which is inversely related to the rotational motion of the probe in membrane phospholipids, was significantly higher at 37 degrees C than at 23 degrees C for 9 series of red blood cells ghosts obtained from three healthy subjects. We also have studied the importance of the nature of two different polaroid films which permits the observation of fluorescence polarization.     

Flip-flop of doxorubicin across erythrocyte and lipid membranes

Doxorubicin, an anticancer drug, is extruded from multidrug resistant (MDR) cells and from the brain by P-glycoprotein located in the plasma membrane and the blood-brain barrier, respectively. MDR-type drugs are hydrophobic and, as such, enter cells by diffusion through the membrane without the requirement for a specific transporter. The apparent contradiction between the presumably free influx of MDR-type drugs into MDR cells and the efficient removal of the drugs by P-glycoprotein, an enzyme with a limited ATPase activity, prompted us to examine the mechanism of passive transport within the membrane. The kinetics of doxorubicin transport demonstrated the presence of two similar sized drug pools located in the two leaflets of the membrane. The transbilayer movement of doxorubicin occurred by a flip-flop mechanism of the drug between the two membrane leaflets. At 37 degrees, the flip-flop exhibited a half-life of 0.7 min, in both erythrocyte membranes and cholesterol-containing lipid membranes. The flip-flop was inhibited by cholesterol and accelerated by high temperatures and the fluidizer benzyl alcohol. The rate of doxorubicin flux across membranes is determined by both the massive binding to the membranes and the slow flip-flop across the membrane. The long residence-time of the drug in the inner leaflet of the plasma membrane allows P-glycoprotein a better opportunity to remove it from the cell.     

Clinical radiopharmacy: principles and practices

It is shown that a series of colchicine-selected multidrug-resistant (MDR) human KB carcinoma cell lines displayed increasing 2-deoxy-D-glucose collateral sensitivity, which correlated with increasing multidrug resistance. The relative resistance of MDR cell lines to 2-deoxy-D-glucose was reduced to 0.73 (KB-8-5), 0.3 (KB-8-5-11) and 0.2 (KB-C1) when compared with parental KB-3-1 (1.0). 2-Deoxy-D-glucose accumulation was found to be reduced in the MDR cell lines in a manner that correlated with 2-deoxy-D-glucose collateral sensitivity. At 30 min 2-deoxy-D-glucose accumulation was reduced to 0.61 (KB-8-5), 0.41 (KB-8-5-11) and 0.22 (KB-C1) relative to KB-3-1 uptake (1.0). The efflux of 2-deoxy-D-glucose was not significantly different between resistant and sensitive cell lines. Analysis of 2-deoxy-D-glucose uptake kinetics, by initial rate measurements, showed alterations in K(t) and J(max) for MDR when compared with KB-3-l cells. The levels of GLUT-1 facilitative transporter were found to be reduced significantly in the MDR cell lines in total cell homogenate and plasma membrane fractions by using Western blot analysis. Changes in the plasma membrane level of GLUT-1 correlated with 2-deoxy-D-glucose toxicity and uptake for MDR cell lines, where relative GLUT-i levels were reduced to 0.71 (KB-8-5), 0.43 (KB-8-5-1 1) and 0.27 (KB-Cl) relative to KB-31(1.0). It is concluded that the response of human KB MDR cells to 2-deoxy-D-glucose involved alterations in the level and activity of the facilitative glucose transporter, GLUT-1, in a manner that is associated with the degree of multidrug resistance.     

Laboratory diagnosis of keratomycosis: comparative evaluation of direct microscopy and culture results

We have studied the variation of lateral diffusion of proteins in the cell membrane, of membrane lipid fluidity and of the electrophoretic motility (EPM) of macrophages after treatment with extrinsic laminin. The results showed that the lateral diffusion coefficient D value of membrane proteins, the fluidity of membrane lipids and the EPM of macrophages were decreased after laminin had bound to its membrane receptor on the macrophages. These results are important for developing an understanding of the early reaction of plasma membranes and cells in the presence of laminin.     

Prostaglandin E2 secretion, cell maturation, and CD14 expression by monocyte-derived macrophages from localized juvenile periodontitis patients

Free eicosapentaenoic acid (EPA) was found to inhibit dose dependently the chemiluminescence of human neutrophil granulocytes phagocytosing zymosan and their chemotaxis induced by C5a-containing zymosan-activated serum (ZAS) and platelet-activating factor. Rigidification of plasma membranes in the ZAS-treated cells could be observed by measuring the fluorescence anisotropy. The cells were labeled by 3-[p-(6-phenyl-1,3,5-hexatrienoil) phenyl] propionic acid, reporting plasma membrane for determination of membrane fluidity. In resting, nonstimulated neutrophils, EPA dose dependently increased the fluidity of plasma membrane. In zymosan-activated cells, however, after a short fluidization, the basic effect of EPA was a rigidification compared to very low fluorescence anisotropy values of activated control cells. This diminished fluidity, increased membrane stability of plasma membranes can be one of the reasons for the decreased functions (phagocytosis and chemotaxis) of human EPA-treated neutrophils.     

The influence of shrinkage-cracking on the drying behaviour of White Portland cement using Single-Point Imaging (SPI)

We examined membrane fluidity of bovine adrenal chromaffin cells and chromaffin granules using cationic trimethylammonium derivative of diphenylhexatriene (TMA-DPH) as a fluorescence probe. After adding TMA-DPH to the suspension of chromaffin cells and that of granules, it first bound to the outer layer of the plasma membrane of the cells and that of the granule membrane, then gradually penetrated the inner layer of each membrane and distributed to both leaflets of the respective membranes. Accompanying increases in the ratio of incorporated probe on the cytoplasmic side of the chromaffin cell membrane, its fluorescence anisotropy gradually decreased. However, in chromaffin granules, the fluorescence anisotropy gradually increased with increases in the ratio of incorporated probe. These findings suggest that the inner layer of the plasma membrane and outer layer of the granular membrane are more fluid than the corresponding side of each membrane, which is suitable for the fusion between both membranes. We also examined the effect of trichosporin-B-VIa, a fungal ion channel forming alpha-aminoisobutyric acid-containing peptide, on the fluidity of chromaffin cells using TMA-DPH. The peptide decreased the fluorescence anisotropy and increased the fluorescence intensity in the concentration range that induced Ca2+ dependent catecholamine secretion, suggesting that a change in lipid dynamics of the lipid bilayer of the plasma membrane was induced by this peptide.     

Increased hepatic Na,K-ATPase activity during hepatic regeneration is associated with induction of the beta1-subunit and expression on the bile canalicular domain

Cellular and molecular mechanisms regulating the activity of the sodium pump or Na,K-ATPase during proliferation of hepatocytes following 70% liver resection have not been defined. Na,K-ATPase may be regulated by synthesis of its alpha- and beta-subunits, by sorting to either the sinusoidal or apical plasma membrane domains, or by increasing membrane lipid fluidity. This study investigated the time course of changes during hepatic regeneration for Na, K-ATPase activity, lipid composition and fluidity, and protein content of liver plasma membrane subfractions. As early as 4 h after hepatic resection, Na,K-ATPase activity was increased selectively in the bile canalicular fraction. It reached a new steady state at 12 h and remained elevated for 2 days. Although hepatic regeneration was associated with a reduced cholesterol/phospholipid molar ratio and increased fluidity, measured with two different probes, these changes in lipid metabolism were in the sinusoidal membrane domain. The Na,K-ATPase beta1-subunit, but not the alpha1-subunit, was increased selectively at the bile canalicular surface as shown by immunoblotting of liver plasma membrane subfractions and the morphological demonstration at both the light and electron microscopic levels. Furthermore, cycloheximide blocked the rise in beta1-subunit mRNA levels. Since the time course for beta1-subunit accumulation was similar to that for activation of Na,K-ATPase activity, this change implicated the beta1-subunit in activating sodium pump activity.     

Increased saturated triacylglycerol levels in plasma membranes of human neutrophils stimulated by lipopolysaccharide

Neutrophils isolated from patients with bacterial infections or stimulated in vitro with lipopolysaccharide (LPS) produce a high resolution, lipid-dominated spectrum on 1H-NMR spectroscopy (May et al, 1993. J. Infect. Dis. 168: 386-392). We have investigated the origin of this lipid signal using NMR and chemical analyses of both whole neutrophils and purified plasma membranes. Plasma membranes from neutrophils that had been stimulated with 50 microg/ml LPS exhibited the high resolution 1H-NMR signal, and contained double the triacylglycerol (TAG) content of plasma membranes isolated from resting cells. Chemical analysis of the whole cells indicated that the TAG also increased at the cellular level (1.7-fold) after stimulation with LPS. Diradylglycerol increased 2- to 3-fold in both whole cells and plasma membranes after stimulation, but was only a minor component compared with TAG. The plasma membrane protein/phospholipid ratio increased 2.6-fold, whereas cholesterol (free and esterified) was unchanged. The membranes from LPS-stimulated neutrophils exhibited increased fluidity, as judged by increased merocyanine 540 binding, consistent with a 2-fold reduction in cholesterol/phospholipid ratio. LPS induced a shift in fatty acid content of whole cell polar lipids towards more oleic acid and less palmitic acid, whereas the neutral lipid fraction contained increased amounts of palmitic and stearic acids. The TAG fraction of plasma membrane lipids contained increased amounts of palmitic acid when prepared from cells stimulated with LPS. We conclude that the 1H-NMR signal in LPS-stimulated neutrophils arises from increased amounts of plasma membrane TAG with an elevated content of palmitic acid.     

Enhanced sensitivity of P-glycoprotein-positive multidrug resistant tumor cells to complement-mediated lysis

The interaction of KB-V1, a multidrug resistant (MDR) variant of the KB-3-1 human oral carcinoma, with human complement was investigated. KB-V1 cells were found to be more sensitive than KB-3-1 cells to complement-mediated lysis. Detailed analysis of the capacity of KB cells to activate human complement demonstrated that both C3b deposition and formation of the membrane attack complex (MAC) are higher on KB-V1 than on KB-3-1 cells. Furthermore, the MAC formed on KB-V1 cells, but not on KB-3-1 cells, was found to be resistant to trypsin treatment, i.e. more stably inserted into the plasma membrane. Immunofluorescence analysis by flow cytometry showed that KB-V1 cells express less decay-accelerating factor (DAF, CD55) than KB-3-1 cells. Two other complement regulatory proteins, membrane cofactor protein (MCP, CD46) and CD59 are expressed to a similar extent on both KB-V1 and KB-3-1 cells. Treatment of KB-V1 cells with neutralizing anti-P-glycoprotein (P-gp) monoclonal antibodies reduced their sensitivity to complement. In addition, KB-V1 revertants which cease to express P-gp become more resistant to complement. These results indicate that multiple factors, such as reduced expression of DAF, enhanced deposition of C3b and increased binding and stability of the MAC may contribute to the increased complement sensitivity of KB-V1 cells. It is suggested that P-gp is responsible for the complement-sensitive phenotype of KB-V1 cells.     

Insulin resistance in adult polycystic kidney disease

Adult polycystic kidney disease (APKD) is a common hereditary disease with renal and extra-renal manifestations. There are at least three genes responsible for this disease. The polycystic kidney disease 1 (PKD1) gene product is a membrane protein involved in cell-cell and cell-matrix interactions and has a widespread tissue distribution. Abnormal membrane fluidity in erythrocytes from APKD patients is due to altered membrane proteins. Membrane fluidity of mononuclear cells is related to whole body insulin sensitivity. Insulin sensitivity might therefore be disturbed in APKD if the erythrocyte membrane abnormality is also present in other cells. Therefore, we investigated insulin sensitivity in 15 APKD patients and 20 normal subjects matched for age and sex. Insulin sensitivity was assessed by a short insulin tolerance test to derive the first-order rate constant for the disappearance of glucose (Kitt) and mononuclear leukocyte membrane fluidity was measured by fluorescence anisotropy. The Kitt value (% mmol.liter-1.min-1) was lower in APKD patients than in normal subjects [median (range) 2.2 (1.5 to 6.3) vs. 4.1 (2.0 to 5.4). P < 0.001]. Fasting plasma insulin concentrations were negatively correlated with the Kitt values (r = -0.66, P < 0.001). Core region anisotropy was significantly lower (higher fluidity) in leukocytes from APKD patients [mean (SEM) 0.164 (0.003) vs. 0.174 (0.001), P < 0.001]. Insulin sensitivity was positively correlated with the fluorescence anisotropy of the core region of leukocyte membranes (r = 0.81, P = 0.0001). In conclusion, APKD patients were insulin resistant and some patients were hyperinsulinemic, which may indicate increased cardiovascular risk. The cellular basis of the insulin resistance may be directly related to the proteins causing the disease or to the general change in membrane properties.     

Detection of metastatic activity of the MCF-7 multidrug resistant cell line cultured in spheroids

The occurrence of solid tumors spreading through the body is a major concern for the clinicians. Moreover, in numerous cases, metastases exhibit a multidrug resistant (MDR) pattern. This dual characteristic still remains supported by few biological explanations. The purpose of our study was to compare invasive properties of sensitive and MDR MCF-7 cells. Spheroids were chosen as experimental model since they exhibit a number of characteristics (i.e. tridimensional structure) close to the growth of an in vivo tumor. MDR spheroids formed more compact structures compared to sensitive ones. In every experiment, spheroids made from sensitive cells were more resistant to doxorubicin than the same cells grown as monolayers, a characteristic not observed with MDR cells. On an other hand, a form of multicellular resistance appeared in spheroids of sensitive cells, a fact which was not present in MDR spheroids. Incubation of MDR spheroids in Boyden's chambers put in evidence increased motility and invasive properties through Matrigel which were not present in sensitive MCF-7 cells. Zymograms of culture media and membrane extracts were performed in polyacrylamide gels. Two metalloproteases, progelatinases A et B were detected in culture media conditioned by monolayers and spheroids of both sensitive and resistant cells. In contrast, 2 unidentified serine proteases were detected only in media conditioned by spheroids of both cell types. An intense band of pro-MMP2 was present only in membrane extracts from MDR spheroids. Taken altogether, these results demonstrate that spheroids of MDR cells exhibit a number of properties which could lead to an increased ability to form metastases.     

Effect of long chain polyunsaturated fatty acids in the sn-2 position of phosphatidylcholine on the interaction with recombinant high density lipoprotein apolipoprotein A-I

The effects of polyunsaturated fatty acids (PUFA) on the structure of recombinant high density lipoprotein (rHDL) was investigated using homogeneous particles containing phosphatidylcholine (PC), [3H]cholesterol, and apolipoprotein A-I (apoA-I). The PC component of the rHDL contained sn -1 16:0 and sn -2 18:1 (POPC), 18:2 (PLPC), 20:4 (PAPC), 20:5 n-3 (PEPC), or 22:6 n-3 (PDPC). The concentration of guanidine HCl (D1/2) required to denature one-half of the apoA-I on rHDL containing long chain PUFA was reduced (1.57-1.70 m) compared to those containing POPC (2.83 m). Intrinsic apoA-I tryptophan fluorescence emission intensity and lifetimes were decreased for rHDL containing long chain PUFA compared to POPC and PLPC rHDL. Monoclonal antibody binding studies demonstrated that apoA-I had decreased immunoreactivity with monoclonal antibodies spanning amino acid residues 115-147 in rHDL containing long chain PUFA. PC lipid fluidity, measured as diphenylhexatriene (DPH) fluorescence polarization, was increased in PUFA rHDL compared to POPC rHDL. There also was a strong correlation between the number of sn -2 double bonds in rHDL and DPH fluorescence lifetime (r 2 = 0. 89). LCAT reactivity of the homogeneous size rHDL was ordered POPC = PLPC>PAPC> PEPC>PDPC. We conclude that rHDL with long chain PUFA in the sn -2 position of PC contain apoA-I that is less stable and in a different conformation than that in POPC rHDL and have a fatty acyl region that is more fluid and hydrated. The weaker interaction of apoA-I with PC containing PUFA may lead to hypercatabolism of apoA-I in plasma explaining, in part, the decreased plasma HDL and apoA-I concentrations seen with PUFA diets.