Implication of BBM lipid composition and fluidity in mitigated alkaline phosphatase activity in renal cell carcinoma

Previous study has documented reduced alkaline phosphatase (ALP) activity in brush border membrane (BBM) isolated from renal cell carcinoma (RCC). Diminished activity of ALP is associated with alteration in both increased K (m) as well as decreased V (max) of enzyme suggests that there may be a change in the conformation of enzyme as well as decreased number of ALP active molecules. The present study was conducted to find out any role of BBM lipid composition and its fluidity in diminished activity of alkaline phosphatase in renal cell carcinoma. Total phospholipids and glycolipids were significantly augmented in BBM from RCC as compared to control. Fractional analysis of total phospholipids revealed significantly increased phosphatidylethanolamine. Decreased fractions of sphingomyelin and phosphatidylinositol were observed. Cholesterol-to-total phospholipid molar ratios in tumor BBM was a significantly lower in tumor BBM. A significant reduction in polarization and microviscosity was found in BBM from RCC. Therefore, we conclude that alteration in membrane lipid composition and fluidity may play a substantial role in reduced activity of ALP in RCC.     

Superoxide dismutase depletion and lipid peroxidation in rat liver microsomal membranes: correlation with liver carcinogenesis

The depletion of superoxide dismutase in the liver of rats held on a copper-deficient diet for 8 weeks induces two profound modifications in microsomal membrane characteristics. These membranes show: (1) a low degree of peroxidation induced in vitro by both endogenous (NADPH and tert-butylhydroperoxide) and exogenous sources (xanthine/xanthine oxidase) of oxygen radicals as revealed by malondialdehyde and diene-conjugate production; (2) a strong decrease of polyunsaturated and an increase of monounsaturated fatty acid content. These alterations are similar to those found in microsomal membranes from fast-growing hepatomas which exhibit a pronounced saturation of fatty acid pattern and lack superoxide dismutase. These observations support the hypothesis that during hepatocarcinogenesis the loss of superoxide dismutase causes an oxidative stress that increases cellular membrane lipid peroxidation, as a consequence of which the cell responds by synthesizing more saturated fatty acids that permanently modify cell membrane structure and properties.     

Phospholipid dependence of rat liver microsomal acyl: CoA synthetase and acyl-CoA : 1-Acyl-sn-glycero-3-phosphocholine O-acyltransferase

Summary Investigations were performed on the influence of the phospholipid composition and physicochemical properties of the rat liver microsomal membranes on acyl-CoA synthetase and acyl-CoA : 1-acyl-sn-glycero-3-phosphocholine O-acyltransferase activities. The phospholipid composition of the membranes was modified by incubation with different phospholipids in the presence of lipid transfer proteins or by partial delipidation with exogenous phospholipase C and subsequent enrichment with phospholipids. The results indicated that the incorporation of phosphatidylglycerol, phosphatidylserine and phosphatidylethanolamine induced a marked activation of acyl-CoA synthetase for both substrates used—palmitic and oleic acids. Sphingomyelin occurred as specific inhibitor for this activity especially for palmitic acid. Palmitoyl-CoA: and oleoyl-CoA : lacyl-sn-glycero-3-phosphocholine acyltransferase activities were found to depend on the physical state of the membrane lipids. The alterations in the membrane physical state were estimated using two different fluorescent probes—1,6-diphenyl-1,3,5-hexatriene and pyrene. In all cases of membrane fluidization this activity was elevated. On the contrary, in more rigid membranes obtained by incorporation of sphingomyelin and dipalmitoylphosphatidylcholine, acyltransferase activity was reduced for both palmitoyl-CoA and oleoyl-CoA. We suggest a certain similarity in the way of regulation of membrane-bound acyltransferase and phospholipase A₂ which both participate in the deacylation-reacylation cycle.     

Alternation of plasma membrane lipids in aluminum-resistant and aluminum-sensitive wheat genotypes in response to aluminum stress

We have studied the effect of aluminum (A1) on lipid composition of plasma membranes from roots of an A1-resistant (PT741) and an A1-sensitive (Katepwa) cultivar of Triticum aestivum L. Several genotype–specific changes were observed in phospholipids and steryl lipids. While exposure to 20 μ M AICI₃ for 3 days had no effect on total phospholipids in either genotype, the most abundant phospholipid, phosphatidylcholine, increased significantly in the A1-sensitive Katepwa. Aluminum also decreased steryl lipids (mainly free sterols) in PT741. Such changes were not observed in Katepwa. As a result of differential changes in lipid composition, the relative abundance of one lipid class to another changed. The ratio of steryl lipids to phospholipids decreased in PT741, with no change in Katepwa. While limited information on the relationship between membrane function and lipid composition makes it difficult to relate these changes to A1 toxicity and resistance, changes observed only in the A1–resistant genotype could contribute to continued plant growth in the face of A1 stress.     

Effects of 2-hydroxyoleic acid on the structural properties of biological and model plasma membranes

Genetic hypertension is associated with alterations in lipid metabolism, membrane lipid composition and membrane-protein function. 2-Hydroxyoleic acid (2OHOA) is a new antihypertensive molecule that regulates the structure of model membranes and their interaction with certain peripheral signalling proteins in vitro. While the effect of 2OHOA on elevated blood pressure is thought to arise through its influence on signalling proteins, its effects on membrane lipid composition remain to be assessed. 2OHOA administration altered the lipid membrane composition of hypertensive and normotensive rat plasma membranes, and increased the fluidity of reconstituted liver membranes from hypertensive rats. In spontaneously hypertensive rats (SHR), treatment with 2OHOA increased the cholesterol and sphingomyelin content while decreasing that of phosphatidylserine-phosphatidylinositol lipids. In addition, monounsaturated fatty acid levels increased as well as the propensity of reconstituted membranes to form H_II-phases. These data suggest that 2OHOA regulates lipid metabolism that is altered in hypertensive animals, and that it affects the structural properties of liver plasma membranes in SHR. These changes in the structural properties of the plasma membrane may modulate the activity of signalling proteins that associate with the cell membrane such as the Gαq/11 protein and hence, signal transduction.     

Ectopic expression of alkaline phosphatase in proximal tubular brush border membrane of human renal cell carcinoma

The present study was conducted to find out any alteration in the expression and activity of alkaline phosphatase in the brush border membrane (BBM) from renal cell carcinoma (RCC) in comparison to normal renal BBM. The specific activity of alkaline phosphatase was drastically reduced in homogenate as well as BBM from RCC kidney when compared to ALP activity in BBM of normal kidney. Kinetic studies revealed that diminished activity of alkaline phosphatase in BBM isolated from RCC was fraternized with decrease in maximal velocity (V(max)) and increase in affinity constant (K(m)) of the enzyme. SDS-PAGE studies showed that the BBM proteins having molecular weights ranging from 95 to 170 kDa were poorly expressed in RCC BBM in relative to normal kidney BBM. Incubation of SDS-PAGE gel with BCIP/NBT dye clearly showed that the expression of ALP in tumor renal BBM was markedly reduced as compared to normal kidney. Further, Western blot analysis using anti-alkaline phosphatase antibody also confirmed the reduced expression of ALP in tumor renal BBM. Lipid composition in reference to phospholipids, glycolipids and cholesterol in tumor renal BBM was altered to that of normal renal BBM, indicating alteration in membrane fluidity of tumor renal BBM.     

Diets alter jejunal morphology and brush border membrane composition in streptozotocin-diabetic rats

Previous studies have demonstrated enhanced active and passive uptake of many nutrients in animals with experimental diabetes. These changes in absorption cannot be explained by differences in intestinal morphology, although the brush border membrane (BBM) phospholipids do change in diabetes. Manipulation of diet produces alterations in intestinal uptake of lipids and glucose. This study was undertaken to determine the effect of diet and diabetes on jejunal morphology and BBM lipid composition. Rats were rendered hyperglycemic with streptozotocin and were fed for 2 weeks on a diet that was high or low in carbohydrate, essential fatty acids, cholesterol, or protein. In both control and diabetic rats, these diets produced changes in villus height and BBM sucrase and alkaline phosphatase activities. In both control and diabetic rats, BBM phospholipids were unaffected by changes in the dietary content of essential fatty acids, cholesterol, or protein, but total BBM phospholipid content was reduced in animals fed low as compared with high carbohydrate diet. Total BBM phospholipid content was higher in diabetic than in control animals fed the low protein diet, whereas BBM phospholipid content was lower in diabetic than in control animals fed the high carbohydrate diet, and was even lower in diabetic animals fed the low as compared with the high carbohydrate diet. These changes in total phospholipids were due to alterations in the BBM content of phospholipids containing choline. In control animals, BBM cholesterol was higher in rats fed the low as compared with the high cholesterol diet, or the low as compared with the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroid hormones stimulate Na+–Pi transport activity in rat renal brush-border membranes: Role of membrane lipid composition and fluidity

Antecedent studies have suggested that lipid composition and fluidity of cellular membranes of various organs are altered in response to thyroid hormone status. To date, the effects of thyroid hormone status on these parameters have not been examined in rat renal apical membrane in regard to sodium-dependent phosphate transport. In the present study, we determined the potential role of alterations in cortical brush-border membrane lipid composition and fluidity in modulation of Na⁺–P_i transport activity in response to thyroid hormone status. Thyroid hormone status influences the fractional excretion of Pi, which is associated with alteration in renal brush-border membrane phosphate transport. The increment in Na⁺–P_i transport in renal BBMV isolated from Hyper-T rats is manifested as an increase in the maximal velocity (V_max) of Na⁺–P_i transport. Further, the cholesterol content was significantly increased in renal BBM of Hypo-T rats and decreased in Hyper-T rats as compared to the Eu-T rats. The molar ratio of cholesterol/phospholipids was also higher in renal BBM from hypo-T rats. Subsequently, fluorescence anisotropy of diphenyl hexatriene (rDPH) and microviscosity were significantly decreased in the renal BBM of the Hyper-T rats and increased in the Hypo-T rats as compared to Eu-T rats. The result of this study, therefore, suggest that alteration in renal BBM cholesterol, cholesterol/phospholipid molar ratio, and membrane fluidity play an important role in the modulation of renal BBM Na⁺–P_i transport in response to thyroid hormone status of animals. (Mol Cell Biochem 268: 75–82, 2005)     

Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.     

Comparison between in vitro lipid peroxidation in fresh sheep platelets and peroxidative processes during sheep platelet ageing under storage at 4 degrees C.

Incubation of sheep platelet crude membranes with xanthine oxidase (XO)/hypoxanthine/Fe(2+)-ADP revealed: (i) a fast peroxidative response - with a maximal linear rate of 14 nmol malondialdehyde (MDA) equivalents/mg protein, as evidenced by the thiobarbituric acid test - and a decrease in the polyunsaturated fatty acid (PUFA) content of the platelet crude membranes; (ii) a decrease in the lipid fluidity in the deep lipid core of the membranes but not at the membrane surface; (iii) a dramatic inhibitory effect on glucose 6-phosphatase (Glc-6-Pase) but not on acetylcholinesterase activity. Platelets were also aged by storage at 4 degrees C in their own plasma or in Seto additive solution. In these media, platelet aggregates were visible and the effects on platelet phospholipids, PUFA, lipid extract fluorescence, crude membrane fluidity and membrane-bound enzyme activities were assessed for comparison with those observed in in vitro lipid peroxidation. The sensitivity of membranes from stored platelets to lipid peroxidation was also assessed. Storage of platelets in plasma for 5 days was associated with different changes in their crude membranes such as decreases in arachidonic acid contents, the decrease not being avoided by the presence of phospholipase A(2) inhibitors, increases in MDA equivalents, conjugated dienes and lipid extract fluorescence, decreases in the amounts of MDA equivalents formed by platelet crude membranes treated with the oxidizing agents, changes in membrane fluidity and inhibition of Glc-6-Pase. All these alterations were less pronounced or even abolished after platelet storage in Seto. These findings suggest that platelet lipid peroxidation due to XO/hypoxanthine/Fe(2+)-ADP and platelet membrane alterations observed after platelet ageing under storage at 4 degrees C share common features. Also, as regards the prevention of peroxidative processes, Seto solution permits better storage of sheep platelets than plasma.     

Age-Related Differences in Synaptosomal Peroxidative Damage and Membrane Properties

Young, adult, and old rats were used to study the effect of age on the integrity and functioning of brain synaptosomes. An evaluation was made of the differences in lipid composition, membrane fluidity, Na+, K(+)-ATPase activity, and susceptibility to in vitro lipid peroxidation. There was an age-related increase in synaptosomal free fatty acids, with no modification in acyl chain composition, and a decrease in membrane phospholipids which increased the cholesterol/phospholipid mole ratio. With altered lipid composition, there was a corresponding age-dependent decrease in membrane fluidity, a reduction of Na+, K(+)-ATPase activity, and an overall greater susceptibility to in vitro lipid peroxidation. Furthermore, lipid peroxidation promoted strong modifications of the membrane fluidity, lipid composition, and Na+,K(+)-ATPase activity just as aging did, thus indicating a possible contribution of oxidative damage to ageing processes. The cases studied revealed that the greater responsiveness of old membranes to in vitro lipid peroxidation resulted in the highest degree of membrane alteration, indicating that all pathological states known to promote a peroxidative injury can have even more dramatic consequences when they take place in old brain.     

Bilirubin induces loss of membrane lipids and exposure of phosphatidylserine in human erythrocytes

Unconjugated bilirubin increasingly binds to erythrocytes as the bilirubin-to-albumin molar ratio exceeds unity, leading to toxic manifestations that can culminate in cell lysis. Our previous studies showed that bilirubin induces the release of lipids from erythrocyte membranes. In the present work, those studies were extended in order to characterize the alterations of membrane lipid composition and evaluate whether bilirubin leads to a loss of phospholipid asymmetry. To this end, human erythrocytes were incubated with several bilirubin-to-albumin molar ratios (0.5 to 5), and cholesterol as well as the total and the individual classes of phospholipids were determined. To detect erythrocytes with phosphatidylserine at the outer surface, the number of annexin V-positive cells was determined following incubation with bilirubin, fixing its molar ratio to albumin at 3. The results demonstrate profound changes in erythrocyte membrane composition, including modified cholesterol and phospholipid content. The release of membrane cholesterol, as well as of total and individual classes of phospholipids at molar ratios ≥1, indicates that damage of erythrocytes may occur in severely ill jaundiced neonates. The loss of the inner-located phospholipids, phosphatidylethanolamine and phosphatidylserine, points to a redistribution of phospholipids in the membrane bilayer. This was confirmed by the exposure of phosphatidylserine at the outer cell surface. In conclusion, this study demonstrates that bilirubin induces loss of membrane lipids and externalization of phosphatidylserine in human erythrocytes. These features may facilitate hemolysis and erythrophagocytosis, thus contributing to enhanced bilirubin production and anemia during severe neonatal hyperbilirubinemia. This revised version was published online in July 2006 with corrections to the Cover Date.     

Inhibition of cell membrane lipid peroxidation by cadmium- and zinc-metallothioneins

The effects of all-zinc metallothionein (Zn-metallothionein) and predominantly cadmium metallothionein (Cd/Zn-metallothionein) on free radical lipid peroxidation have been investigated, using erythrocyte ghosts as the test system. When treated with xanthine and xanthine oxidase, Zn-metallothionein and Cd/Zn-metallothionein underwent thiolate group oxidation and metal ion release that was catalase-inhibitable, but superoxide dismutase-non-inhibitable. Similar treatment in the presence of ghosts and added Fe(III) resulted in metallothioneen oxidation that was significantly inhibited by superoxide dismutase. Ghosts incubated with xanthine/xanthine oxidase/Fe(III) underwent H₂O₂- and O₂⁻-dependent lipid peroxidation, as measured by thiobarbituric acid reactivity. Neither type of metallothionein had any effect on xanthine oxidase activity, but both strongly inhibited lipid peroxidation when added to the membranes concurrently with xanthine/xanthine oxidase/iron. This inhibition was far greater and more sustained than that caused by dithiothreitol at a concentration equivalent to that of metallothionein thiolate. Significant protection was also afforded when ghosts plus Cd/Zn-metallothionein or Zn/metallothionein were preincubated with H₂O₂ and Fe(III), and then subjected to vigorous peroxidation by the addition of xanthine and xanthine oxidase. These results could be mimicked by using Cd(II) or Zn(II) alone. Previous studies suggested that Zn(II) inhibits xanthine/xanthine oxidase/iron-driven lipid peroxidation in ghosts by interfering with iron binding and redox cycling. Therefore, the primary determinant of metallothionein proteciion appears to be metal release and subsequent uptake by the membranes. These results have important implications concerning the antioxidant role of metallothionein, a protein known to be induced by various prooxidant conditions.     

Liver ischemia increases the molecular order of microsomal membranes by increasing the cholesterol-to-phospholipid ratio

An accelerated degradation of phospholipid is the likely basis of irreversible cell injury in ischemia, and the membranes of the endoplasmic reticulum of the liver are a convenient system with which to study the effect of such a disturbance on the structure and function of cellular membranes. In the present report, electron spin resonance spectroscopy has been used to evaluate changes in the molecular ordering of microsomal membrane phospholipids in the attempt to relate the loss of lipid to alterations in membrane structure. The order parameter, S, was calculated from spectra reflecting the anisotropic motion of 12-doxyl stearic acid incorporated into normal and 3-h ischemic microsomal membranes. Over the temperature range 4-40 degrees C, the molecular order (S) of ischemic membranes was increased by 8-10%. This increase was reproduced in the ordering of the phospholipids in liposomes prepared from total lipid extracts of the same membranes. In contrast, after removal of the neutral lipids, liposomes prepared from phospholipids of ischemic and control membranes had the same molecular order. There were no differences in the phospholipid species of control and ischemic membranes or in the fatty acid composition of the phospholipids. In the neutral lipid fraction of ischemic membranes, however, triglycerides and cholesterol were increased compared to control preparations. There were no free fatty acids. The total cholesterol content of the liver was unchanged after 3 h of ischemia. The cholesterol-to-phospholipid ratio of ischemic membranes, however, was increased by 22% from 0.258 to 0.315 as a consequence of the loss of phospholipid. Addition of cholesterol to the control total lipid extracts to give a cholesterol-to-phospholipid ratio the same as in ischemic membranes resulted in liposomes with order parameters similar to those of liposomes prepared from ischemic total lipids. It is concluded that the degradation of the phospholipids of the microsomal membrane results in a relative increase in the cholesterol-to-phospholipid ratio. This is accompanied, in turn, by an increased molecular order of the residual membrane phospholipids.     

Functional changes in bladder tissue from type III collagen-deficient mice

The present work investigates the protective effects of N-acetylcysteine (NAC) on carbofuran-induced alterations in lipid composition and activity of membrane bound enzymes (Na⁺-K⁺-ATPase and Ca²⁺-ATPase) in the rat brain. Animals were exposed to carbofuran at a dose of 1 mg/kg body weight, orally, for a period of 28 days. A significant increase in lipid peroxidation in terms of TBARS was observed in brain after carbofuran exposure. NAC administration (200 mg/kg body weight) on the other hand lowered the carbofuran-induced lipid peroxidation to near normal. The increased lipid peroxidation following carbofuran exposure was accompanied by a significant decrease in the levels of total lipids, which is attributed to the reduction in phospholipid levels. Furthermore, NAC administration had a beneficial effect on carbofuran-induced alterations in lipid composition. The ratio of cholesterol to phospholipid, a major determinant of membrane fluidity, was increased in response to carbofuran exposure. This was associated with decreased activity of Na⁺-K⁺-ATPase and Ca²⁺-ATPase. NAC was observed to offer protection by restoring the cholesterol to phospholipid ratio along with the activity of Na⁺-K⁺-ATPase and Ca²⁺-ATPase. The results clearly suggest that carbofuran exerts its neurotoxic effects by increasing lipid peroxidation, altering lipid composition and activity of membrane bound enzymes. NAC administration ameliorated the effects of carbofuran suggesting its potential therapeutic effects in carbofuran neurotoxicity.     

Chronic cold stress-induced alterations in brush border membrane composition and enzyme activities in rat intestine

The effect of chronic cold stress on the composition and function of rat intestinal brush border membrane (BBM) was studied. Various lipid fractions from intestinal BBM viz. cholesterol (p < 0.01), phospholipids (p < 0.01), triglycerides (p < 0.05) and gangliosides (p < 0.05) were significantly reduced in cold stressed animals, as compared to controls. Analysis of membrane saccharide content revealed a significant increase in sialic acid (25%) and hexosamine (36%) contents and a reduction in fucose (19%) content in cold stressed rats. Determination of various enzyme activities in BBM showed significantly enhanced activities of alkaline phosphatase ( p < 0.01), lactase ( p < 0.001) and leucine aminopeptidase ( p < 0.001), whereas sucrase activity was reduced ( p < 0.05) under these conditions. The magnitude and site of these alterations across the crypt-villus axis varied from enzyme to enzyme. These findings suggest that chronic cold stress results in profound alterations in intestinal BBM. Altered structure and function of intestinal BBM may play a role in stress-induced derangements in gastrointestinal tract.     

Different modes of ozone-induced lipid oxidation in Candida utilis yeast cells and isolated membrane preparations

Significant differences in the development of ozonolysis of lipids in membrane preparations and intact cells of the Candida utilis yeast were revealed. First, unlike isolated membranes, in which lipid modifications can be initiated by low ozone doses (< 0.5 micromol O3/mg protein) and develop proportionally to the treatment dose, in intact yeast cells, even the most ozone-sensitive sterols and nitrogen-containing phospholipids (phosphatidylcholine and phosphatidylethanolamine) did not undergo oxidative destruction at doses up to 6.0 micromol O3/mg protein. Second, the peculiarity of the ozone-initiated lipid modification in intact cells was that different classes of lipids exhibited different sensitivity to ozone. With an increase in the ozone dose, neutral lipids (sterols) and nitrogen-containing phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin) were modified to a greater extent. Third, the accumulation of lipid peroxidation products upon ozone treatment of cells, in contrast to the isolated membranes, was absent at low ozone doses and was recorded only after the lethal damage. It is suggested that these differences are related to both the function of antioxidative enzymes (catalase, superoxide dismutase, peroxidase, etc.) and the difference between the structural states (i.e., stability and accessibility to oxidation) of lipids in the isolated membranes and the intact cells.     

Effect of ionizing radiation on the lipid fatty acid composition of the plasma membranes of liver cells

Changes in the fatty acid composition of total lipids and individual phospholipids of liver cell plasma membranes of intact and exposed (7.65 Gy) rats have been studied. The authors discuss the relationship between the degree of lipid oxidation and other lipid characteristics of the studied membrane after exposure to ionizing radiation.     

Resection of rabbit ileum: effect on brush border membrane enzyme markers and lipids

Alterations in transport function have been described 6 weeks after surgical resection of 50% of the distal small intestine. Previous studies demonstrated a modest increase in the jejunal uptake of medium chain length fatty acids following resection, while the uptake of many other lipids (cholesterol, bile acids, fatty alcohols, short and long chain length fatty acids) appears to be unaffected. Marked changes in the kinetic constants for the carrier-mediated uptake of four sugars and leucine were observed following resection, but the changes in transport were not associated with changes in the mucosal surface area. This study was undertaken to examine the possible adaptive mechanisms that occur with ileal resection in the rabbit. A 29% increase in the wet weight of jejunal mucosal scrapings and a 53% increase in jejunal brush border membrane (BBM) protein was observed following resection. The jejunal BBM sucrase (S) was unchanged following ileal resection, but alkaline phosphatase (AP) total activities were increased in the resected rabbits. This resulted in a 45% increase in the ratio of AP/S with resection. The lipid composition (total free fatty acids, total bile acids, total cholesterol, total phospholipids, individual phospholipids, and the ratio of total phospholipids/total cholesterol) of BBM was similar in control and resected rabbits. This suggests that quantitative rather than qualitative changes in the membrane composition may be responsible for the transport changes observed in resected animals.     

Radiation-induced lipid peroxidation: influence of oxygen concentration and membrane lipid composition

Radiation-induced lipid peroxidation in phospholipid liposomes was investigated in terms of its dependence on lipid composition and oxygen concentration. Non-peroxidizable lipid incorporated in the liposomes reduced the rate of peroxidation of the peroxidizable phospholipid acyl chains, possibly by restricting the length of chain reactions. The latter effect is believed to be caused by interference of the non-peroxidizable lipids in the bilayer. At low oxygen concentration lipid peroxidation was reduced. The cause of this limited peroxidation may be a reduced number of radical initiation reactions possibly involving oxygen-derived superoxide radicals. Killing of proliferating mammalian cells, irradiated at oxygen concentrations ranging from 0 to 100 per cent, appeared to be independent of the concentration of peroxidizable phospholipids in the cell membranes. This indicates that lipid peroxidation is not the determining process in radiation-induced reproductive cell death.