| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Plasma lipoprotein cholesterol levels in rats fed a diet enriched in cholesterol and cholic acid Chiang, M. T., Y. C. Chen, et al. (1998), Int J Vitam Nutr Res 68(5): 328-34. Abstract: To investigate the effects of dietary cholesterol and cholic acid on plasma cholesterol levels, rats fed a cholesterol-free diet or a diet enriched in cholesterol (0.5% or 1%) with or without cholic acid supplementation were studied for 4 weeks. Although 0.5% cholesterol supplementation showed no effect on plasma total cholesterol and LDL-cholesterol levels in rats fed a diet without cholic acid treatment, the addition of dietary cholic acid caused an increase in plasma total cholesterol, LDL-cholesterol and VLDL-cholesterol levels in rats fed a cholesterol-rich diet. There was no significant change in HDL-cholesterol levels among the dietary groups. Rats fed a diet enriched in cholesterol have increased liver total lipids and total cholesterol contents. In addition, lower liver lipid peroxide concentration was found in rats fed a cholesterol-rich diet when compared with those fed the control diet. It is interesting that cholic acid supplementation led to an increase in hepatic cholesterol content and a decrease in liver lipid peroxide concentration in rats fed a cholesterol-rich diet. Results from this study suggest that dietary cholesterol and cholic acid might play an important role in regulation of lipid metabolism in rats. |
| Plasma lipoproteins affect rate of cholesterol absorbed from bile by gallbladder: preliminary data Della Guardia, P., A. Grossi, et al. (1999), Ital J Gastroenterol Hepatol 31(7): 587-92. Abstract: BACKGROUND: The excessive accumulation of cholesterol absorbed from bile by the gallbladder impairs its contractility and favours gallstone formation. The total low plasma and high density lipoprotein cholesterol concentrations are associated with gallstone disease. AIMS: To investigate the effect of plasma lipoproteins on gallbladder cholesterol and phosphatidylcholine absorption from bile and to establish whether cholesterol absorption is Brefeldin A-sensitive. METHODS: Gallbladder mucosa lipid absorption rates were measured using: 1) in vitro isolated intra-arterially perfused pig gallbladder model with and without plasma lipoproteins perfusing the vascular tree; 2) human gallbladder fragments mounted in Ussing chambers with plasma lipoproteins at different concentrations in the serosal side; 3) pig gallbladder fragments mounted in Ussing chambers in the presence and absence of Brefeldin A. RESULTS: Total lipoproteins and high density lipoprotein significantly increased the release of biliary cholesterol and phosphatidylcholine in plasma and significantly decreased the tissue accumulation of cholesterol absorbed from bile. The scavenger effect of plasma lipoproteins on cholesterol absorbed from bile was concentration dependent. Brefeldin A did not influence gallbladder absorption of biliary cholesterol. CONCLUSIONS: Biliary cholesterol is absorbed by gallbladder mucosa via a Brefeldin-insensitive pathway and is removed by plasma lipoproteins. |
| Plasma lipoproteins after triglyceride clearance in cholesterol-fed rats Quarfordt, S. H., B. S. Oswald, et al. (1993), J Clin Invest 91(6): 2532-8. Abstract: The clearance of particulate triglyceride from the plasma of cholesterol-fed rats with appreciable stores of hepatic cholesterol ester produces a substantial increment in plasma cholesterol. Most of this plasma cholesterol increment arises from existing tissue sources. The increment begins from 4 to 6 h after clearance and is due to the appearance of larger cholesterol-rich, triglyceride-poor, beta migrating lipoproteins, which are isolated in the d < 1.063 fraction with an apoprotein (Apo) content consisting primarily of Apo E and smaller amounts of Apo B. A concurrent decrease in alpha lipoproteins occurs with the beta lipoprotein increment. Within 1 d of clearance the beta lipoproteins fall and alpha lipoproteins increase. The increase in total plasma Apo E and Apo B initially parallels that of the cholesterol, but it persists even when cholesterol falls. A modest decrease in plasma Apo A1 was observed during the time alpha lipoproteins declined. A significant increase in plasma lecithin cholesterol acyl transferase preceded the increase in beta lipoprotein cholesterol. This enzyme increment was absent in rats with little lipoprotein response despite increased hepatic cholesterol. In vivo inhibition of this enzyme with dithionitrobenzoic acid virtually eliminated the postclearance hypercholesterolemia. Plasma particulate triglyceride clearance induces an increase in beta lipoproteins. Coupling of this clearance and hepatic lipoprotein secretion occurs by an unknown mechanism modulated by lecithin cholesterol acyl transferase. |
| Plasma lipoproteins and cholesterol metabolism in Yoshida rats: an animal model of spontaneous hyperlipemia Fantappie, S., A. L. Catapano, et al. (1992), Life Sci 50(24): 1913-24. Abstract: The purpose of this study was to characterize the lipoprotein profile and cholesterol metabolism in Yoshida rats, a strain of inbred genetically hyperlipemic animals. For comparison, Brown Norway rats were used as control animals. Plasma cholesterol and triglycerides were higher in Yoshida as compared to Brown Norway, the elevation of cholesterol being due to a rise in HDL fraction. Triglyceride distribution among lipoproteins showed an increase in VLDL fraction. Hyperlipemia was not related to diabetes, hypothyroidism or nephropathy. Plasma triglycerides production was increased in Yoshida rats, while lipoprotein and hepatic lipases were similar in the two groups. Hypercholesterolemia was associated with a defect of lipoprotein receptor activity and with elevated HMG-CoA reductase and cholesterol 7 alpha - hydroxylase; conversely ACAT activity was lower in Yoshida as compared to Brown Norway rats. Sterol fecal excretion was comparable in the two groups and hypercholesterolemia in Yoshida rats was not associated to an increase of cholesterol saturation of the bile. We suggest that lipoprotein overproduction is the main cause for hyperlipidemia in this strain of rats. |
| Plasma lipoproteins and incidence of non-insulin-dependent diabetes mellitus in Pima Indians: protective effect of HDL cholesterol in women Fagot-Campagna, A., K. M. Narayan, et al. (1997), Atherosclerosis 128(1): 113-9. Abstract: The role of plasma lipoproteins in the development of non-insulin-dependent diabetes mellitus (NIDDM) was studied in 787 non-diabetic (2-h glucose < 11.1 mmol/l) Pima Indians (265 men and 522 women). Subjects were followed for a mean of 9.8 (range: 1.8-16.4) years, during which 261 (76 men and 185 women) developed NIDDM. In men and women, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, low-density lipoprotein triglyceride and total triglyceride, controlled for age, predicted NIDDM (P < 0.01 for each). These effects diminished when controlled for age, sex, body mass index, systolic blood pressure and 2-h glucose. However, high-density lipoprotein (HDL) cholesterol, controlled for age, body mass index, systolic blood pressure and 2-h glucose, was a significant protective factor for NIDDM in women (hazard rate ratio (HRR) = 0.35, 95% CI (0.23-0.54), P < 0.001, 90th compared with 10th percentile) but not in men (HRR = 1.04, 95% CI (0.53-2.05), P = 0.915). This association remained significant in women when controlled for fasting or 2-h plasma insulin concentrations, other estimates of insulin resistance or alcohol consumption. The protective effect of HDL cholesterol was similar among women with normal (2-h glucose < 7.8 mmol/1) or impaired (7.8 mmol/l < or = 2-h glucose < 11.1 mmol/l) glucose tolerance at baseline. These results indicate that lipoprotein disorders are an early accompaniment of the abnormalities that lead to NIDDM. |
| Plasma lipoproteins in preruminant calves fed diets containing tallow or soybean oil with and without cholesterol Leplaix-Charlat, L., D. Bauchart, et al. (1996), J Dairy Sci 79(7): 1267-77. Abstract: Five-week-old, preruminant male calves were fed milk replacer containing tallow or soybean oil (230 g/ kg of dietary DM) with and without cholesterol (10 g/ kg of dietary DM) for 17 d in order to study changes in plasma lipids and lipoproteins. Dietary soybean oil induced higher cholesterolemia than did tallow because of a specific increase in plasma concentrations of large high density lipoproteins of type 1 (1.026 to 1.060 g/ml), but plasma concentrations of low and very low density lipoproteins were not modified. Addition of cholesterol to diets containing either tallow or soybean oil markedly increased plasma concentrations of intermediate and low density lipoproteins, suggesting partial inhibition of the low density lipoprotein receptor activity in tissue. By contrast, dietary cholesterol added to the diet containing soybean oil led to an increase in plasma concentrations of type 1 high density lipoproteins and of light high density (1.060 to 1.091 g/ml) lipoproteins. These data indicated that the soybean oil diet, which was rich in linoleic acid, did not reduce the effects of dietary cholesterol on the metabolism of low and high density lipoproteins in the preruminant calf. |
| Plasma low density lipoprotein cholesterol concentration in cynomolgus monkeys; differing effects of age and body weight in animals consuming low and high cholesterol diets Colvin, P. L., Jr., B. J. Spray, et al. (1994), Atherosclerosis 111(2): 191-7. Abstract: It has been reported in cross-sectional studies that plasma cholesterol concentration does not increase with age in nonhuman primates who consume a cholesterol-free diet over their lifetimes. However, dietary composition and body weight may confound any change in plasma cholesterol concentration during aging, as is the case in humans in industrialized societies. To determine if the relationship between age and plasma cholesterol concentration is affected by dietary cholesterol and body weight in nonhuman primates, we compared post-pubertal male cynomolgus monkeys consuming low cholesterol (0.04 mg cholesterol/kcal; n = 10) and high cholesterol (0.39 mg cholesterol/kcal: n = 21) diets. A univariate repeated measures analysis of covariance of low density lipoprotein (LDL) cholesterol concentration was performed from a longitudinal data set (monkeys aged 5 to 20 years), containing an average of 34 observations per animal. The interaction of age and body weight on LDL cholesterol concentration differed among the two dietary groups. In monkeys consuming the low cholesterol diet, an increase in age was associated with a small increase in mean LDL cholesterol concentration. This effect of age increased with increasing body weight. Monkeys on the high cholesterol diet had higher mean LDL concentration, but showed no significant effect of aging on concentration. Instead, at all ages, LDL concentration was strongly affected (positively) by body weight in this group. A qualitatively similar (but quantitatively smaller) effect of body weight was observed only at older ages in the low dietary cholesterol group. We conclude that the associations of LDL concentration with age and body weight in cynomolgus monkeys are strongly influenced by dietary cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Plasma low-density lipoprotein cholesterol and bone mass densitometry in postmenopausal women Poli, A., F. Bruschi, et al. (2003), Obstet Gynecol 102(5 Pt 1): 922-6. Abstract: OBJECTIVE: The prevalence and the clinical and social importance of osteopenia and osteoporosis are increasing in western societies. To improve knowledge of the risk factors associated with these conditions, we assessed the relationship between bone mass density and plasma lipid profile in a cohort of postmenopausal women. METHODS: We studied 1303 postmenopausal women who attended a menopause outpatient clinic. All women underwent bone mineral density determination at the level of the lumbar spine. Plasma lipids and lipoproteins and bone metabolic markers were assessed on a blood sample obtained after a 12-hour fast. RESULTS: Statistically significant associations were found by univariate analysis between prevalence of osteopenia and age, time since menopause, body mass index, and low-density lipoprotein (LDL) cholesterol. Specifically, women with plasma LDL cholesterol levels of at least 160 mg/dL had a more than doubled probability of being osteopenic compared with women with lower LDL cholesterol (47.9% versus 21.2%, respectively). Time since menopause, body mass index, and LDL cholesterol were the only variables significantly associated with the prevalence of osteopenia, by multivariable analysis. CONCLUSION: Postmenopausal women with increased plasma LDL cholesterol levels had a greater probability of being classified as osteopenic than women with normal plasma LDL cholesterol levels. Our data, if confirmed, suggest that elevated levels of plasma LDL cholesterol should be regarded as an additional risk factor for reduced bone mineral density. |
| Plasma lycopene concentrations in humans are determined by lycopene intake, plasma cholesterol concentrations and selected demographic factors Mayne, S. T., B. Cartmel, et al. (1999), J Nutr 129(4): 849-54. Abstract: Higher plasma lycopene concentrations have been associated with a reduced risk of several chronic diseases. Determinants of lycopene concentrations in humans have received limited attention. We had blood lycopene concentrations and lycopene consumption data available from 111 participants in a two-center cancer prevention trial involving beta-carotene and examined determinants of plasma lycopene levels cross-sectionally. The median plasma lycopene level was 0.59 micromol/L (range 0.07-1.79). Low plasma concentrations of lycopene were associated with the following variables in univariate analyses: study site (Florida lower than Connecticut, P = 0.001), being nonmarried (P = 0.02), having lower income (P = 0.003), being nonwhite race/ethnicity (P = 0.03), having lower dietary lycopene intake (r = 0.29, P = 0.002), having lower plasma cholesterol (r = 0. 43, P = 0.0001) and triglyceride levels (r = 0.26, P = 0.005), and consuming less vitamin C (r = 0.20, P = 0.03). Women had slightly higher plasma lycopene levels than men (0.65 vs. 0.58 micromol/L; P = 0.31), despite lower dietary intake of lycopene (1,040 vs. 1,320 microg/d; P = 0.50). Plasma lycopene levels did not differ in smokers and nonsmokers. In stepwise regression analyses, the determinants of plasma lycopene were plasma cholesterol, dietary lycopene, and marital status; these three variables explained 26% of the variance in plasma lycopene. Relatively few lifestyle and demographic factors were important determinants of plasma lycopene levels, with plasma cholesterol, marital status, and lycopene intake being of greatest importance. |
| Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome Chan, D. C., G. F. Watts, et al. (2003), Obes Res 11(4): 591-6. Abstract: OBJECTIVE: The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality. RESEARCH METHODS AND PROCEDURES: We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling. RESULTS: Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption. DISCUSSION: Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome. |
| Plasma membrane caveolae mediate the efflux of cellular free cholesterol Fielding, P. E. and C. J. Fielding (1995), Biochemistry 34(44): 14288-92. Abstract: Caveolae are clathrin-free cell-surface organelles implicated in transmembrane transport. A fibroblast caveolar membrane fraction was isolated by sucrose density gradient ultracentrifugation and its identity confirmed by protein markers (caveolin, annexin II). When 3H-labeled free cholesterol was selectively transferred to the cells from labeled low density lipoprotein to increase cell free cholesterol approximately 15%, there was a 6-fold increase in label in the caveolar fraction above baseline levels. Subsequent incubation of these cells with unlabeled native plasma or plasma high density lipoprotein selectively unloaded caveolar free cholesterol into the medium. Okadaic acid, which decreased caveolar activity as measured by cholera toxin binding and uptake, decreased cholesterol efflux in parallel. Cholesterol newly synthesized from 3Hmevalonate was also preferentially incorporated into the caveolar fraction and selectively released by plasma into the medium. Together these data indicate that caveolae represent a major site of efflux of both newly synthesized and low density lipoprotein-derived free cholesterol in these cells. |
| Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AbetaP (1-40) and (1-42) peptides Arispe, N. and M. Doh (2002), Faseb J 16(12): 1526-36. Abstract: Cell degeneration in Alzheimer's disease is mediated by a toxic mechanism that involves interaction of the AbetaP peptide with the plasma membrane of the target cell. We report here that PC12 cells become resistant to the cytotoxic action of AbetaP when incubated in a medium that enriches cholesterol levels of the surface membrane. On the other hand, making cholesterol-deficient membranes by either cholesterol extraction with cyclodextrin or by inhibiting de novo synthesis of cholesterol makes PC12 cells more vulnerable to the action of AbetaP. Increasing cholesterol content of PS liposomes also suppresses AbetaP-dependent liposome aggregation. We suggest that by modifying the fluidity of the neuronal membranes, cholesterol modulates the incorporation and pore formation of AbetaP into cell membranes. This idea is supported by our finding that the enhanced cytotoxicity generated by lowering the membrane cholesterol content can be reversed by AbetaP calcium channel blockers Zn2+ and tromethamine. |
| Plasma membrane cholesterol is a key molecule in shear stress-dependent activation of extracellular signal-regulated kinase Park, H., Y. M. Go, et al. (1998), J Biol Chem 273(48): 32304-11. Abstract: Shear stress, the dragging force generated by fluid flow, differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in bovine aortic endothelial cells (BAEC) (Jo, H., Sipos, K., Go, Y. M., Law, R., Rong, J., and McDonald, J. M. (1997) J. Biol. Chem. 272, 1395-1401). Here, we examine whether cholesterol-enriched compartments in the plasma membrane are responsible for such differential regulation. Pretreatment of BAEC with a cholesterol-binding antibiotic, filipin, did not inhibit shear-dependent activation of JNK. In contrast, filipin and other membrane-permeable cholesterol-binding agents (digitonin and nystatin), but not the lipid-binding agent xylazine, inhibited shear-dependent activation of ERK. The effect of cholesterol-binding drugs did not appear to be due to membrane permeabilization, since treatment of BAEC with a detergent, Triton X-100 which also permeabilizes membranes, did not inhibit shear-dependent activation of ERK. Furthermore, shear-dependent activation of ERK, but not JNK, was inhibited by cyclodextrin, a membrane-impermeable cholesterol-binding agent, which removes cell-surface cholesterol. Moreover, the effects of cyclodextrin were prevented by adding cholesterol during the incubation. These results indicate that cholesterol or cholesterol-sensitive compartments in the plasma membrane play a selective and essential role in activation of ERK, but not JNK, by shear stress. Although exposure to shear stress (1 h) increased the number of caveolae by 3-fold, treatment with filipin had no effect in either control or shear-exposed cells suggesting that caveolae density per se is not a crucial determinant in shear-dependent ERK activation. In summary, the current study suggests that cholesterol-sensitive microdomains in the plasma membrane, such as caveolae-like domains, play a critical role in differential activation of ERK and JNK by shear stress. |
| Plasma membrane cholesterol is utilized as steroidogenic substrate in Y-1 mouse adrenal tumor cells and normal sheep adrenal cells Gocze, P. M. and D. A. Freeman (1993), Exp Cell Res 209(1): 21-5. Abstract: Previous studies from this laboratory indicate that plasma membrane cholesterol acts as an important source of steroidogenic substrate for MA-10 Leydig tumor cells. The present studies were designed to generalize these findings to other steroidogenic cells and to another species. Studies were performed using the Y-1 murine adrenal tumor cell line and primary cultures of sheep adrenocortical cells. Treating Y-1 cells with the acyl coenzyme A:cholesterol acyltransferase inhibitor, 58-035, caused cellular cholesteryl ester depletion and rendered more apparent the effect of dibutyryl-cAMP to cause cellular free cholesterol depletion. Radioactive 20 alpha-dihydroprogesterone was synthesized by Y-1 cells that had been plasma membrane-labeled with 3H-cholesterol. Primary sheep adrenal cultures that had been cholesteryl ester-depleted also demonstrated cellular free cholesterol depletion after stimulation with dibutyryl cAMP. Plasma membrane label was converted to steroid hormones in these cells as well. Taken together, these data indicate that the use of plasma cholesterol is not restricted to the MA-10 cells. The present data indicate that both neoplastic mouse adrenal tumor cells and normal sheep adrenal cells utilize plasma membrane cholesterol. |
| Plasma membrane cholesterol modulates cellular vacuolation induced by the Helicobacter pylori vacuolating cytotoxin Patel, H. K., D. C. Willhite, et al. (2002), Infect Immun 70(8): 4112-23. Abstract: The Helicobacter pylori vacuolating cytotoxin (VacA) induces the degenerative vacuolation of mammalian cells both in vitro and in vivo. Here, we demonstrate that plasma membrane cholesterol is essential for vacuolation of mammalian cells by VacA. Vacuole biogenesis in multiple cell lines was completely blocked when cholesterol was extracted selectively from the plasma membrane by using beta-cyclodextrins. Moreover, increasing plasma membrane cholesterol levels strongly potentiated VacA-induced vacuolation. In contrast, inhibiting de novo biosynthesis of cholesterol with lovastatin or compactin had no detectable effect on vacuolation. While depletion of plasma membrane cholesterol has been shown to interfere with both clathrin-mediated endocytosis and caveola-dependent endocytosis, neither of these two internalization pathways was found to be essential for vacuolation of cells by VacA. Depleting plasma membrane cholesterol attenuated the entry of VacA into HeLa cells. In addition, beta-cyclodextrin reagents blocked vacuolation of cells that were either preloaded with VacA or had VacA directly expressed within the cytosol. Collectively, our results suggest that plasma membrane cholesterol is important for both the intoxication mechanism of VacA and subsequent vacuole biogenesis. |
| Plasma membrane cholesterol: a critical determinant of cellular energetics and tubular resistance to attack Zager, R. A. (2000), Kidney Int 58(1): 193-205. Abstract: BACKGROUND: Cholesterol is a major component of plasma membranes, forming membrane microdomains ("rafts" or "caveolae") via hydrophobic interactions with sphingolipids. We have recently demonstrated that tubule cholesterol levels rise by 18 hours following diverse forms of injury, and this change helps to protect kidneys from further damage (so-called acquired cytoresistance). The present study was undertaken to better define the effects of membrane cholesterol/microdomains on tubule homeostasis and cell susceptibility to superimposed attack. METHODS: Plasma membrane cholesterol was perturbed in normal mouse proximal tubular segments with either cholesterol esterase (CE) or cholesterol oxidase (CO). Alternatively, cholesterol-sphingomyelin complexes were altered by sphingomyelinase (SMase) treatment. Changes in cell energetics (ATP/ADP ratios + ouabain), viability lactate dehydrogenase (LDH) release, phospholipid profiles, and susceptibility to injury (Fe-induced oxidant stress, PLA2, Ca2+ ionophore) were determined. The impacts of selected cytoprotectants were also assessed. RESULTS: Within 15 minutes, CE and CO each induced approximately 90% ATP/ADP ratio suppressions. These were seen prior to lethal cell injury (LDH release), and it was ouabain resistant (suggesting decreased ATP production, not increased consumption). SMase also depressed ATP without inducing cell death. After 45 minutes, CE and CO each caused marked cytotoxicity (up to 70% LDH release). However, different injury mechanisms were operative since (1) CE, but not CO, toxicity significantly altered cell phospholipid profiles, and (2) 2 mmol/L glycine completely blocked CE- but not CO-mediated cell death. Antioxidants also failed to attenuate CO cytotoxicity. Disturbing cholesterol/microdomains with a sublytic CE dose dramatically increased tubule susceptibility to Fe-mediated oxidative stress and Ca2+ overload, but not PLA2-mediated damage. CONCLUSION: Intact plasma membrane cholesterol/microdomains are critical for maintaining cell viability both under basal conditions and during superimposed attack. When perturbed, complex injury pathways can be impacted, with potential implications for both the induction of acute tubular damage and the emergence of the postinjury cytoresistance state. |
| Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal and mutant CHO cells defective in cholesterol metabolism Khan, N., J. Shen, et al. (2003), Biochemistry 42(1): 23-9. Abstract: The effect of the cholesterol content of the plasma membrane on the intracellular concentration of oxygen in Chinese hamster ovary (CHO) cells and their mutants was investigated by EPR oximetry. Total and free cholesterol content was significantly higher in 25 RA CHO cells as compared to wild-type and M 19 CHO cells, with most of the free cholesterol in normal and mutant CHO cells located in the plasma membrane. The plasma membrane cholesterol content also was altered by various biochemical means, and the effect on the oxygen gradient was studied. Comparing the three cell lines, the gradient was larger with increased content of cholesterol in the plasma cell membrane. This result also is supported by an additional increase in the oxygen gradients with the incorporation of additional cholesterol in the plasma membrane and a decrease in the oxygen gradient when the cholesterol was depleted from the plasma membrane. The results indicate that the concentration of cholesterol in the plasma membrane can be an important factor for the magnitude of the oxygen gradient observed across the cell membrane. |
| Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naive patients at the onset of psychosis Mahadik, S. P., S. Mukherjee, et al. (1994), Schizophr Res 13(3): 239-47. Abstract: Contents of plasma membrane major phospholipids, cholesterol, and cholesteryl esters of fibroblasts from drug-naive psychotic patients were compared with those from normal controls. Total membrane lipids were extracted and individual lipids were separated on high-performance thin-layer chromatography. The contents of lipid bands were quantitated by densitometric scanning and comparing with standards. Contents of total phospholipids as well as phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine were significantly lower in fibroblasts from patients than in those from normal controls (P < 0.001, < 0.005, < 0.05 respectively). Total cholesterol fraction and cholesteryl esters were also significantly lower in fibroblasts from patient (P < 0.005, < 0.001 respectively). These changes were not related to differences in age or sex. These data support the hypothesis that schizophrenia is associated with disordered membrane lipid metabolism, and that this predates the onset of psychosis. |
| Plasma membrane sphingomyelin and the regulation of HMG-CoA reductase activity and cholesterol biosynthesis in cell cultures Gupta, A. K. and H. Rudney (1991), J Lipid Res 32(1): 125-36. Abstract: We have examined the mechanism of the inhibition of cholesterol synthesis in cells treated with exogenous sphingomyelinase. Treatment of rat intestinal epithelial cells (IEC-6), human skin fibroblasts (GM-43), and human hepatoma (HepG2) cells in culture with sphingomyelinase resulted in a concentration- and time-dependent inhibition of the activity of HMG-CoA reductase, a key regulatory enzyme in cholesterol biosynthesis. The following observations were obtained with IEC-6 cells. Free fatty acid synthesis or general cellular protein synthesis was unaffected by the addition of sphingomyelinase. Addition of sphingomyelinase to the in vitro reductase assay had no effect on activity, suggesting that an intact cell system is required for the action of sphingomyelinase. The products of sphingomyelin hydrolysis, e.g., ceramide and phosphocholine, had no effect on reductase activity. Sphingosine, a further product of ceramide metabolism, caused a stimulation of reductase activity. Examination of the incorporation of 3Hacetate into the nonsaponifiable lipid fractions in the presence of sphingomyelinase showed no changes in the percent distribution of radioactivity in the post-mevalonate intermediates of the cholesterol biosynthetic pathway, but there was increased radioactivity associated with the polar sterol fraction. Pretreatment of cells with ketoconazole, a known inhibitor of oxysterol formation, prevented the inhibition of reductase activity by sphingomyelinase and decreased the incorporation of 3Hacetate in the polar sterol fraction. Ketoconazole had no effect on exogenous sphingomyelinase activity in vitro in the presence or absence of cells. Endogenous sphingomyelinase activity was also unaffected by ketoconazole. Addition of inhibitors of endogenous sphingomyelinase activity, e.g., chlorpromazine, desipramine, and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), to the culture medium caused a dose-dependent stimulation of reductase activity. However, these agents had no effect on the inhibition of reductase activity by exogenous sphingomyelinase. Treatment of cells with small unilamellar vesicles of dioleyl phosphatidylcholine or high density lipoprotein3 resulted in increased efflux of cholesterol and stimulation of reductase activity. Under similar conditions, the inhibitory effect of exogenous sphingomyelinase on reductase activity was prevented by incubation with small unilamellar vesicles of phosphatidylcholine or high density lipoprotein. These results support the hypothesis that alteration of the ratio of sphingomyelin:cholesterol in the plasma membrane plays a modulatory role on the flow of membrane cholesterol to a site where it may be converted to a putative regulatory molecule, possibly an oxysterol. |
| Plasma membrane steroidogenic cholesterol: the relative importance of membrane internalization rate and cholesterol extraction rate of internalized membrane Freeman, D. A., A. Romero, et al. (1998), Endocr Res 24(3-4): 619-22. Abstract: Most cholesterol destined to become steroid hormone passes through the plasma membrane. Using MA-10 Leydig tumor cells as a model system, we determined that plasma membrane cholesterol disappeared 2.5-fold faster in cAMP-stimulated cells. Stimulation of MA-10 cells increased internalization so that 1.4-fold more membrane cycled through the cell per unit time. Increased internalization accounted for 26% of the cholesterol actually lost from cycling membrane. The remaining 74% was accounted for by increasing the extraction of cholesterol from internalized membrane. |