| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Protein kinase C as a mediator of high density lipoprotein receptor-dependent efflux of intracellular cholesterol Mendez, A. J., J. F. Oram, et al. (1991), J Biol Chem 266(16): 10104-11. Abstract: The interaction of high density lipoproteins (HDL) with the HDL receptor stimulates the translocation of cholesterol from intracellular pools to the plasma membrane where the cholesterol becomes available for removal by appropriate acceptors. The role of signal transduction through protein kinase C in HDL receptor-dependent cholesterol translocation and efflux was examined using cholesterol-loaded cultured human skin fibroblasts. Treatment of cells with HDL3 activated protein kinase C, demonstrated by a transient increase in membrane associated kinase activity. Kinase activation appeared to be dependent on binding of HDL3 to the HDL receptor, since tetranitromethane-modified HDL3, which does not bind to the receptor, was without effect. Translocation of intracellular sterol to the plasma membrane was stimulated by treatment of cells with the protein kinase C activators, dioctanoylglycerol and phorbol myristic acetate, and the calcium ionophore A23187. Conversely, treatment of cells with sphingosine, a protein kinase C inhibitor, reduced HDL3-mediated translocation and efflux of intracellular sterols. However, sphingosine had no effect on efflux of labeled cholesterol derived from the plasma membrane. Down-regulation of cellular protein kinase C activity by long term incubation with phorbol esters also inhibited HDL3-mediated efflux of intracellular sterols and abolished the ability of sphingosine to further inhibit HDL3-mediated efflux. These studies support the conclusion that HDL receptor-mediated translocation and efflux of intracellular cholesterol occurs through activation of protein kinase C. |
| Protein kinase C is not involved in cholesterol-induced resistance to synthetic ether lipids Diomede, L., M. Salmona, et al. (1993), Anticancer Res 13(5A): 1331-4. Abstract: The possible role of protein kinase C in cholesterol-induced resistance to ether lipids was investigated. The enrichment of HL60 cells in cholesterol (CHOL) (HL60-CHOL) resulted in a significant increase in the ID50 values for 1-octadecyl-2-methyl-rac-glycero- 3-phosphocholine (ET-18-OMe) (3.75 +/- 0.7 microM and 6.69 +/- 0.5 microM for HL60 and HL60-CHOL, respectively). In the same conditions, HL60 and HL60-CHOL cells showed comparable levels of both cytosolic and membrane-associated protein kinase C activity. Phorbol ester (PMA) stimulation induced protein kinase C to translocate from the cytosol to the plasma membrane in both cell types and with similar kinetics (272 +/- 32% and 299 +/- 41% increase in HL60 and HL60-CHOL, respectively after 100 ng/ml PMA for 10 min). Pretreatment of the two cell types with 50 microM ET-18-OMe resulted in comparable levels of PKC inhibition after phorbol ester stimulation. These results suggested that alterations in plasma membrane lipid composition induced by CHOL do not result in major changes in protein kinase C activity. Thus, protein kinase C does not appear to be involved in cholesterol-induced resistant phenotype in HL60 cells. |
| Protein lipid interaction in bile: effects of biliary proteins on the stability of cholesterol-lecithin vesicles Luk, A. S., E. W. Kaler, et al. (1998), Biochim Biophys Acta 1390(3): 282-92. Abstract: The nucleation of cholesterol crystals is an obligatory precursor to cholesterol gallstone formation. Nucleation, in turn, is believed to be preceded by aggregation and fusion of cholesterol-rich vesicles. We have investigated the effects of two putative pro-nucleating proteins, a concanavalin A-binding protein fraction and a calcium-binding protein, on the stability of sonicated small unilamellar cholesterol-lecithin vesicles. Vesicle aggregation is followed by monitoring absorbance, and upon addition of the concanavalin A-binding protein fraction the absorbance of a vesicle dispersion increases continuously with time. Vesicle fusion is probed by a fluorescence contents-mixing assay. Vesicles apparently fuse slowly after the addition of the concanavalin A-binding protein, although inner filter effects confound the quantitative measurement of fusion rates. The rates of change of absorbance and fluorescence increase with the concentration of the protein, and the second-order dimerization rate constant increases with both the protein concentration and the cholesterol content of the vesicles. On the other hand, the calcium-binding protein has no effect on the stability of the vesicle dispersion. This protein may therefore affect cholesterol crystal formation not by promoting the nucleation process, but by enhancing crystal growth and packaging. Our results demonstrate that biliary proteins can destabilize lipid vesicles and that different proteins play different roles in the mechanism of cholesterol gallstone formation. |
| Protein mediated cholesterol absorption in locusts Schistocerca gregaria (Forskal) and Locusta migratoria (Linn) Upadhyay, R. K., H. C. Agarwal, et al. (2002), Indian J Exp Biol 40(2): 151-61. Abstract: Absorption and transport of 3H cholesterol from the midgut to hemolymph and other tissues was studied in the locusts Schistocerca gregaria and Locusta migratoria. S. gregaria are able to absorb dietary cholesterol in the midgut and release into the hemolymph in vivo and into the incubation medium in virto. Certain proteins of midgut origin are involved in the absorption and release of cholesterol. The proteins designated as cholesterol binding proteins (CBP's) were fractionated by gel filtration chromatography using Sepharose CL-6B-200 column. Presence of a protein and its binding with cholesterol is confirmed by TCA precipitation after subsequent incubation of midgut in the incubation medium. Cholesterol binding with the proteins was also confirmed in native polyacrylamide gel electrophoresis. Biosynthesis of this protein takes place in the midgut which is inhibited by a protein synthesis inhibitor, cycloheximide. It also inhibits absorption and release of cholesterol from the midgut. The cholesterol binding activity was associated with a peak containing proteins ranging from molecular weights of 17-32 kDa in SDS-PAGE gels. Treatment of midgut with cycloheximide resulted in reduced cholesterol binding activity. Dilipidation of mucin and transport in presence of bile salts yielded a higher cholesterol binding activity. Although the absorption and release of cholesterol was observed in the hemolymph of both sexes, the ovary exhibited higher cholesterol binding as compared to testis. |
| Protein phosphatase 1 and 2A inhibitors activate acyl-CoA:cholesterol acyltransferase and cholesterol ester formation in isolated rat hepatocytes Hernandez, M. L., M. J. Martinez, et al. (1997), Biochim Biophys Acta 1349(3): 233-41. Abstract: Okadaic acid, calyculin A and cantharidin, potent and specific inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), stimulated both acyl-CoA:cholesterol acyltransferase (ACAT) activity and cholesterol ester formation in suspension cultures of isolated rat hepatocytes. The activation of microsomal ACAT was marked (up to 14-fold the basal values), fast in onset (within 5 min), persistent in duration (up to 45 min) and concentration-dependent. Concentrations of okadaic acid (OA) or calyculin A > or = 100 nM or of cantharidin > or = 1 microM were required to stimulate enzyme activity, which specifically points to a dominant contribution of PP1. No effects were seen with up to 1 microM nor-okadaone, an inactive OA analogue. Rises in 3Holeate incorporation into cell cholesteryl esters closely paralleled those in ACAT activity, though were somewhat less accentuated. The increases in microsomal ACAT activity seen in OA-, calyculin A- or cantharidin-treated hepatocytes were not linked to changes in bulk microsomal unesterified cholesterol or in the de novo cholesterol synthesis. The findings firmly indicate a role for protein phosphatase activity, probably that of PP1, in controlling the cholesterol esterification rate and ACAT activity in intact rat hepatocytes, which is not secondary to an alteration of the steady-state distribution of cholesterol mass between cell membranes. However, as the OA-induced stimulation of ACAT was not abrogated by addition of purified PP1 or PP2A to microsomes, it is unlikely that the phosphatase inhibitors here used act directly on the phosphorylation degree of the ACAT enzyme. |
| Protein-disulfide isomerase is a component of an NBD-cholesterol monomerizing protein complex from hamster small intestine Cai, T. Q., Q. Guo, et al. (2002), Biochim Biophys Acta 1581(3): 100-8. Abstract: A rapid in vitro assay was developed for monitoring protein-mediated cholesterol monomerization from bile acid aggregates. This assay uses a fluorescent cholesterol analog, 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3 beta-ol (NBD-cholesterol), which was shown to be absorbed by hamster in a fashion similar to cholesterol. The fluorescence of aggregates of NBD-cholesterol was strongly quenched in 2.5 mM of taurocholic acid. Addition of proteins from enterocytes of hamster small intestine led to a time- and dose-dependent dequenching of NBD-cholesterol fluorescence. Comparable dequenching can be detected with SDS and appears to involve monomerization of the NBD-cholesterol. Purification of enterocyte extract by sequential chromatography revealed an approximately 140-kDa protein complex (p140) able to mediate the monomerization of NBD-cholesterol. Each p140 complex mediated monomerization of 2.7 NBD-cholesterol molecules. The p140 complex appeared to be formed by dimerization of two approximately 58-kDa molecules since SDS-PAGE revealed a single dominant band at 58 kDa (p58). Protein sequence analysis suggested that p58 is protein-disulfide isomerase (PDI), and this conclusion was confirmed by cloning of hamster PDI, and detection of PDI enzyme activity in the purified fraction. Additional studies with either pure PDI or lysates of cells transfected with hamster PDI showed that PDI by itself was not sufficient for monomerizing cholesterol. Further, despite a similar mobility on SDS-PAGE (approximately 58 kDa), the p140 complex appeared approximately 45-kDa larger than pure PDI (approximately 95 kDa) when analyzed by a gel-filtration chromatography. The p140 complex may thus contain an unidentified molecule(s) in addition to PDI that may contribute importantly to cholesterol monomerization. |
| Protein-induced formation of cholesterol-rich domains Epand, R. M., S. Maekawa, et al. (2001), Biochemistry 40(35): 10514-21. Abstract: A major protein of neuronal rafts, NAP-22, binds specifically to cholesterol. We demonstrate by circular dichroism that NAP-22 contains a significant amount of beta-structure that is not sensitive to binding of the protein to membranes, suggesting that a major portion of the protein does not insert deeply into the membrane. The free energy of binding of NAP-22 to liposomes of dioleoylphosphatidylcholine with 40% cholesterol is -7.3 +/- 0.5 kcal/mol. NAP-22 mixed with dipalmitoylphosphatidylcholine and 40% cholesterol partitions into the detergent insoluble fraction in the presence of 1% Triton X-100. NAP-22 also causes this insoluble fraction to become enriched in cholesterol relative to phospholipid, again demonstrating the ability of this protein to segregate cholesterol and phospholipids into domains. Differential scanning calorimetry results demonstrate that NAP-22 promotes domain formation in liposomes composed of cholesterol and phosphatidylcholine. This is shown by NAP-22-promoted changes in the shape and enthalpy of the phase transition of phosphatidylcholine as well as by the appearance of cholesterol crystallite transitions in membranes composed of phosphatidylcholine with either saturated or unsaturated acyl chains. In situ atomic force microscopy revealed a marked change in the surface morphology of a supported bilayer of dioleoylphosphatidylcholine with 0.4 mole fraction of cholesterol upon addition of NAP-22. Prior to the addition of the protein, the bilayer appears to be a molecularly smooth structure with uniform thickness. Addition of NAP-22 resulted in the rapid formation of localized raised bilayer domains. Remarkably, there was no gross disruption or erosion of the bilayer but rather simply an apparent rearrangement of the lipid bilayer structure due to the interaction of NAP-22 with the lipid. Our results demonstrate that NAP-22 can induce the formation of cholesterol-rich domains in membranes. This is likely to be relevant in neuronal membrane domains that are rich in NAP-22. |
| Protein-lipid interactions and Torpedo californica nicotinic acetylcholine receptor function. 2. Membrane fluidity and ligand-mediated alteration in the accessibility of gamma subunit cysteine residues to cholesterol Narayanaswami, V. and M. G. McNamee (1993), Biochemistry 32(46): 12420-7. Abstract: Fluorescence-quenching and energy-transfer measurements were carried out to further characterize lipid-protein interactions involving the nicotinic acetylcholine receptor (AChR) from Torpedo californica in reconstituted membranes. To assess the fluidity of the receptor microenvironment, cis- and trans-parinaric acids were used to take advantage of the preferential partitioning behavior of the trans isomer for the gel phase. A relatively higher extent of energy transfer from the intrinsic tryptophan fluorescence of AChR in dielaidoylphosphatidylcholine bilayers to cis-parinaric acid in both the gel and the fluid phase suggests that the AChR is surrounded by a relatively fluid annulus of lipids. The ability of AChR to accommodate and interact with specific lipids such as cholesterol and fatty acids in the vicinity of pyrene-labeled cysteine residues in the membranous domain and/or the membrane-water interface region of the gamma subunit was assessed. Pyrene-labeled AChR prepared in (6,7-dibromostearoyl)phosphatidylcholine showed a 25% decrease in fluorescence as sites accessible to phospholipids were occupied; subsequent addition of dibromocholesterol hemisuccinate (DiBrCHS) caused further quenching by about 25%. This result is consistent with the presence of sites accessible to cholesterol, but not accessible to phospholipids, in the vicinity of the cysteine-bound pyrene in the membranous domain of the AChR. Quenching by DiBrCHS was sensitive to the presence of an AChR activator (carbamylcholine) but not a competitive antagonist (alpha-bungarotoxin). The Stern-Volmer quenching constant was 0.123 in the absence of added ligands and 0.167 and 0.134 in the presence of carbamylcholine and alpha-bungarotoxin, respectively, corresponding to accessibilities of 65%, 90%, and 70%. |
| Protein-lipid interactions in reconstituted high density lipoproteins: apolipoprotein and cholesterol influence Dergunov, A. D., G. E. Dobretsov, et al. (2001), Chem Phys Lipids 113(1-2): 67-82. Abstract: Two fluorescent probes-cis- and trans-parinaric acids were used to study the dimensions, lipid dynamics and apolipoprotein location in the reconstituted discoidal high density lipoproteins (rHDL). The rHDL particles made from apolipoprotein A-I (apoA-I), dipalmitoylphosphatidylcholine (DPPC), with or without cholesterol (Chol) were compared with the analogous particles with two other apolipoproteins-apoE and apoA-II. The data obtained for apoA-I-containing rHDL were as follows: (1) the inclusion of 8 mol.% of cholesterol did not significantly change the particle dimensions (13+/-1 nm) or the mean distance between apoA-I and the disc axis; (2) the phospholipid domains-boundary lipid region in the close vicinity to apoA-I molecule and the remaining part of the bilayer-existed at temperatures both lower and above DPPC transition temperature T(t); (3) at T |
| Proteins of peripheral myelin are associated with glycosphingolipid/cholesterol-enriched membranes Hasse, B., F. Bosse, et al. (2002), J Neurosci Res 69(2): 227-32. Abstract: A characteristic feature of the vertebrate nervous system is the ensheathment of axons by myelin, a multilamellar membrane specialization produced by polarized glial cells. Although the main protein and lipid components of the myelin sheath are well characterized, relatively little is known about the mechanisms of their intracellular distribution to the respective sites of assembly within the myelin sheath. To analyze whether peripheral myelin protein trafficking is mediated by glycosphingolipid/cholesterol-enriched membranes (GEMs), we studied the association of established myelin proteins, peripheral myelin protein 22 (PMP22), protein zero (P0), plasmolipin, and myelin basic protein (MBP), with these membrane microdomains. To examine the association of the selected peripheral myelin proteins with detergent-insoluble GEMs, purified myelin from sciatic nerve of adult rat was extracted with Triton X-100 at 4 degrees C and 37 degrees C and, in additional experiments, was pretreated with the cholesterol chelator methyl-beta-cyclodextrin. The material was then centrifuged to equilibrium in sucrose gradients, and fractions were analyzed by Western blotting. Here we demonstrate for the first time that PMP22, P0, and plasmolipin prepared from purified peripheral myelin are associated with GEMs. To characterize whether the association of these proteins is a specialized feature of myelinating Schwann cells, we studied the distribution of PMP22, P0, and plasmolipin in transiently transfected HeLa cells. These experiments confirm the specific association of these proteins with GEMs in both neural and nonneural cell types. |
| Proteinuria is preceded by decreased nitric oxide synthesis and prevented by a NO donor in cholesterol-fed rats Attia, D. M., Z. N. Ni, et al. (2002), Kidney Int 61(5): 1776-87. Abstract: BACKGROUND: Hypercholesterolemia decreases nitric oxide (NO) availability in the circulation and induces podocyte activation and renal injury in rats. It is unknown whether hypercholesterolemia decreases renal NO availability. To dissociate the injury-independent effect of hypercholesterolemia on renal NO availability from secondary effects of proteinuria, increasing concentrations of cholesterol were administered. To determine whether podocyte activation and renal injury were associated with NO deficiency, molsidomine, an exogenous NO donor, was administered to hypercholesterolemic rats. METHODS: Female rats were fed 0, 0.5, 1, or 2% cholesterol for 24 weeks. Rats fed 2% cholesterol were also studied for two weeks. In addition rats fed 0 or 1% cholesterol received 120 mg molsidomine/L drinking water. Renal NO availability was determined by measuring renal NO synthesis and superoxide activity. Podocyte activation was monitored by desmin staining. RESULTS: Hypercholesterolemia dose-dependently increased proteinuria. In the absence of proteinuria, hypercholesterolemia decreased renal NO synthesis (4.2 +/- 0.5 in 0.5% cholesterol vs. 6.8 +/- 0.6 pmol/min/mg protein in controls; P < 0.05). With the exception of neuronal nitric oxide synthase (nNOS), renal NOS protein mass remained unaffected. Renal superoxide activity was dose-dependently increased, thus further lowering renal NO availability. Podocyte injury was dose-dependently increased even in the absence of proteinuria (score, 40 +/- 4 in 0.5% cholesterol vs. 9 +/- 4 in controls; P < 0.05). After two weeks, hypercholesterolemia caused no proteinuria, but did cause some podocyte injury. Renal NOS activity was decreased, but glomerular endothelial NOS (eNOS) staining was unchanged. Molsidomine prevented proteinuria, podocyte activation, and all further renal injury. CONCLUSIONS: Hypercholesterolemia decreases renal NO synthesis, and induces podocyte activation before proteinuria appears. Renal superoxide activity is increased once rats are proteinuric, further lowering renal NO availability. All of these changes can be prevented by a NO donor. |
| Proteoglycans produced by cholesterol-enriched macrophages bind plasma low density lipoprotein Owens, R. T. and W. D. Wagner (1991), Atherosclerosis 91(3): 229-40. Abstract: Proteoglycans (PG) produced by 35Ssulfate and 3Hserine labeled cultures of cholesterol-enriched macrophages obtained from atherosclerosis-susceptible White Carneau (WC) and -resistant Show Racer (SR) pigeons were characterized and assessed for their capacity to bind low density lipoprotein (LDL). The majority of 35S-labeled PG was released into the culture media in both WC and SR macrophage cultures and consisted of large and small size PG as determined by Sepharose CL-4B chromatography. Large PG were identified as chondroitin sulfate-PG comprised of 4-sulfated disaccharides whereas small PG consisted of primarily 4-sulfated chondroitin sulfate-PG and lesser amounts of heparin sulfate-PG. Experiments demonstrated that 32-34% of 35S-labeled large PG and 86-93% of small PG bound to LDL-substituted Sepharose. Interactions between PG and LDL-substituted Sepharose were inhibited in the presence of heparin or soluble LDL. Glycosaminoglycans derived from macrophage PG had a decreased binding affinity demonstrating the importance of an intact PG. The results suggest that macrophage PG may facilitate trapping of LDL in the intimal intima and promote foam cell formation through a mechanism involving the uptake of PG-LDL complexes. |
| Proteomic characterisation of neuronal sphingolipid-cholesterol microdomains: role in plasminogen activation Ledesma, M. D., J. S. Da Silva, et al. (2003), Brain Res 987(1): 107-16. Abstract: Sorting of certain membrane proteins requires a mechanism involving rafts, protein-lipid complexes enriched in glycosphingolipids and cholesterol. These microdomains remain at the plasma membrane of different cell types and play a role in signal transduction. Although recent reports have begun to describe molecules associated with rafts, their protein composition remains largely unknown, especially in neuronal cells. To address this question, we have purified detergent-insoluble raft fractions (DRMs) from primary cultures of hippocampal neurons. Bidimensional gel analysis and pharmacological raft lipid manipulation allowed the identification of neuronal raft proteins and their characterisation by MALDI-TOF analysis. Enolases were found among the proteins identified and functional studies demonstrate their participation in plasminogen binding. We also show the specific enrichment in rafts of several other plasminogen binding molecules and the exclusive activation of plasminogen to the protease plasmin in these microdomains. These observations suggest that neuronal rafts may play, in addition to intracellular signaling, a role in extracellular/membrane protein proteolysis. |
| Proton nuclear magnetic resonance studies on the molecular dynamics of plasmenylcholine/cholesterol and phosphatidylcholine/cholesterol bilayers Han, X. L. and R. W. Gross (1991), Biochim Biophys Acta 1063(1): 129-36. Abstract: Physiologically relevant molecular species of plasmenylcholine and phosphatidylcholine were synthesized and their molecular dynamics and interactions with cholesterol were compared by determination of salient proton spin-lattice relaxation times and apparent activation energies for 1H-NMR observable motion. The molecular dynamics of PA PhosCho (1-hexadecanoyl-2-eicosatetra-5',8',11',14'-enoyl-sn-glycero-3-pho sphocholine) in multiple regions of the bilayer. Furthermore, the fluidity gradient of PA PhosCho was larger than that of PA PlasCho as ascertained by 1H spin-lattice relaxation time measurements. Introduction of cholesterol into each bilayer resulted in disparate effects on the dynamics of each subclass including: (1) increased motional freedom in the polar head group of PA PlasCho without substantial alterations in the dynamics of the polar head group of PA PhosCho; and (2) increased immobilization of the membrane interior in PA PlasCho in comparison to PA PhosCho. Analysis of Arrhenius plots of T1 relaxation times demonstrated that the apparent activation energies for vinyl and bisallylic methylene proton NMR observable motion in PA PhosCho were greater than that in PA PlasCho. Thus, comparisons of spin-lattice relaxation times and apparent activation energies demonstrate that vesicles comprised of PA PlasCho and PA PhosCho possess differential molecular dynamics and distinct interactions with cholesterol. Collectively, these results underscore the significance of the conjoint presence of the vinyl ether linkage and arachidonic acid as an important determinant of membrane dynamics in specialized mammalian membranes. |
| Providing progesterone for pregnancy: control of cholesterol flux to the side-chain cleavage system Strauss, J. F., 3rd, L. K. Christenson, et al. (2000), J Reprod Fertil Suppl 55: 3-12. Abstract: Progesterone, which is required to support human gestation, is derived initially from the corpus luteum and subsequently from the placenta. The rate-limiting step in progesterone synthesis is the delivery of cholesterol to the mitochondrial cholesterol side-chain cleavage system. The steroidogenic acute regulatory protein (StAR) mediates this process in the corpus luteum, whereas in the placenta, which does not express StAR, a StAR homologue, MLN64, may accomplish this function. StAR expression is regulated in the ovary at the transcriptional level by a cAMP-activated signal transduction system and StAR activity is also increased acutely by protein kinase A-mediated phosphorylation. These long-term (transcriptional) and short-term (post-translational, that is, phosphorylation) mechanisms govern luteal steroidogenic activity. The StAR protein has two key functional domains. The StAR C-terminal domain increases cholesterol movement to cytochrome P450scc by promoting sterol desorption from the sterol-rich outer mitochondrial membrane, driving it to the relatively sterol-poor inner membrane. The N-terminal domain mitochondrial targeting sequence directs the StAR protein to the mitochondria. |
| Proximal tubular cholesterol loading after mitochondrial, but not glycolytic, blockade Zager, R. A., A. C. Johnson, et al. (2003), Am J Physiol Renal Physiol 285(6): F1092-9. Abstract: Diverse forms of injury cause proximal tubular cholesterol accumulation. However, underlying mechanisms in general, and those involved with ATP depletion injury in particular, remain poorly defined. To help elucidate this issue, cholesterol homeostasis and its determinants were assessed after partial ATP depletion states. Serum-exposed HK-2 cells were subjected to mild ATP depletion, induced by mitochondrial inhibition (antimycin A; AA) or glycolytic blockade (2-deoxyglucose; DG). Four or 18 h later, cell cholesterol levels, hydroxymethylglutaryl (HMG)-CoA reductase (HMGCR), the LDL receptor (LDL-R), and ABCA1/SR-B1 cholesterol transporters were assessed. AA and DG each induced mild, largely sublethal ATP depletion injury. Each also caused significant HMGCR increments and SR-B1 decrements and left ABCA1 intact. In contrast, only AA increased the LDL-R, and only AA evoked a cholesterol-loading state (approximately 25% up). One-half of this increase was statin inhibitable, and one-half could be blocked by serum deletion, implying that both synthetic and nonsynthetic (e.g., LDL-R transport) pathways were involved. The AA-induced HMGCR and LDL-R protein changes were paralleled by their mRNAs, suggesting the presence of altered transcriptional events. We conclude that 1) sublethal ATP depletion, whether induced by mitochondrial or glycolytic blockade, can upregulate HMGCR and decrease SR-B1, and these changes represent a previously unrecognized ATP depletion "phenotype"; 2) mitochondrial blockade can also upregulate the LDL-R and evoke a cholesterol-loading state; 3) the latter likely occurs via synthetic and transport pathways; and 4) the mitochondrion may be a critical, and previously unrecognized, determinant of postinjury cell cholesterol homeostasis, potentially by impacting the LDL-R. |
| Pseudochylothorax or cholesterol pleural effusions Rodriguez Gonzalez-Moro, J. M. and J. L. Izquierdo Alonso (1995), Arch Bronconeumol 31(8): 431. |
| Pseudohypopyon of cholesterol crystals occurring 16 years after retinal detachment in x-linked retinoschisis Mielke, J., N. Freudenthaler, et al. (2001), Klin Monatsbl Augenheilkd 218(11): 741-3. Abstract: BACKGROUND: Cholesterol crystals of the anterior chamber can be found as a marked feature of advanced cholesterosis bulbi; typically following i. o. hemorrhage after severe trauma, retinal detachment or M. Coats. CASE REPORT: A 39-year-old male patient with longstanding (16 years) retinal detachment in his right eye due to x-chromosomal linked retinoschisis presented with a clinical picture of a hypopyon and mature cataract. Ultrasonography showed a retrolental mass. Phacolytic uveitis was suspected and pars plana lentectomy and vitrectomy was performed. Intraoperatively subretinal chrystals could be detected. A specimen of the aqueous humor and subretinal fluid was evaluated biochemically and histologically and revealed cholesterol crystals. CONCLUSIONS: Cholesterosis bulbi may be similar to lentogenic uveitis and should be included in the differential diagnosis of such processes. To our knowledge this is the first case of cholesterol crystals of the anterior chamber sixteen years after retinal detachment in x-linked retinoschisis. |
| Pseudopregnancy-dependent accumulation of cholesterol sulfate due to up-regulation of cholesterol sulfotransferase and concurrent down-regulation of cholesterol sulfate sulfatase in the uterine endometria of rabbits Momoeda, M., Y. Cui, et al. (1994), J Biochem (Tokyo) 116(3): 657-62. Abstract: The uterine endometria of rabbits induced into pseudopregnancy by intramuscular injection of 17 beta-estradiol, followed by intravenous injection of human chorionic gonadotropin, expressed cholesterol sulfate at a significantly high concentration. The highest concentration of cholesterol sulfate was observed 4 days after the injection of gonadotropin for formation of the corpus luteum, being 10 times higher than that in nonpregnant endometria, and 15.2% of the total cholesterol in the endometrium was converted to the sulfated form, whose percentage in nonpregnant endometrium was 3.2%. However, no significant change in the concentration of gangliosides was observed during the period of pseudopregnancy. In the pseudopregnant endometria, the activity of cholesterol sulfotransferase, a cytosolic thiol enzyme, was increased thirtyfold over that in the nonpregnant endometria, whereas cholesterol sulfate sulfatase, a microsomal enzyme, exhibited approximately one-tenth of the activity in nonpregnant endometria. Arylsulfatase C, but not arylsulfatases A and B, exhibited the same change in activity as cholesterol sulfate sulfatase. Thus, the striking increase in cholesterol sulfate after induction of pseudopregnancy was found to be due to the activation of cholesterol sulfotransferase and the simultaneous inhibition of cholesterol sulfate sulfatase. |
| Pseudo-ternary phase diagrams of aqueous mixtures of Quil A, cholesterol and phospholipid prepared by the lipid-film hydration method Demana, P. H., N. M. Davies, et al. (2004), Int J Pharm 270(1-2): 229-39. Abstract: Pseudo-ternary phase diagrams of the polar lipids Quil A, cholesterol (Chol) and phosphatidylcholine (PC) in aqueous mixtures prepared by the lipid film hydration method (where dried lipid film of phospholipids and cholesterol are hydrated by an aqueous solution of Quil A) were investigated in terms of the types of particulate structures formed therein. Negative staining transmission electron microscopy and polarized light microscopy were used to characterize the colloidal and coarse dispersed particles present in the systems. Pseudo-ternary phase diagrams were established for lipid mixtures hydrated in water and in Tris buffer (pH 7.4). The effect of equilibration time was also studied with respect to systems hydrated in water where the samples were stored for 2 months at 4 degrees C. Depending on the mass ratio of Quil A, Chol and PC in the systems, various colloidal particles including ISCOM matrices, liposomes, ring-like micelles and worm-like micelles were observed. Other colloidal particles were also observed as minor structures in the presence of these predominant colloids including helices, layered structures and lamellae (hexagonal pattern of ring-like micelles). In terms of the conditions which appeared to promote the formation of ISCOM matrices, the area of the phase diagrams associated with systems containing these structures increased in the order: hydrated in water/short equilibration period |