Effect of erythropoietin on the lipid composition of red blood cell membrane

Effect of Ep on [14C]acetate incorporation into different lipid fractions of RBC membranes in starved and phenylhydrazine-treated rats was studied. The incorporation was increased into both neutral and phospholipid fractions on Ep treatment to starved or phenylhydrazine-treated rats. A slight decrease in the ratio of neutral lipid to phospholipid was observed under the influence of Ep in starved rats (23%) or in phenylhydrazine-treated rats (36%). Incorporation of radioactivities into different phospholipid fractions of RBC membrane increased on Ep treatment to starved rats, whereas, the relative percentages of these phospholipids (except LPC) remained more or less unchanged under similar conditions. Phenylhydrazine treatment increased the relative percentage of PC and concomitantly decreased the percentage of Sph. Percentage composition of both these two phospholipids showed a tendency to return to their normal levels on administration of Ep to phenylhydrazine-treated rats. Ep decreased the sigma saturated/sigma unsaturated ratio of fatty acids in PE, PS, and PC of RBC membrane in starved rats. On the other hand, no significant change was observed in this ratio of fatty acids in the phospholipids except Sph of RBC membrane in the presence of phenylhydrazine and Ep. In Sph, the ratio went down under similar conditions.     

Phosphorylation of phospholipids in isolated guinea pig hearts stimulated with isoprenaline.

Phosphorylation of phospholipids was studied in Langendorff perfused guinea pig hearts subjected to beta-adrenergic stimulation. Hearts were perfused with Krebs-Henseleit buffer containing [32P]Pi and freeze-clamped in a control condition or at the peak of the inotropic response to isoprenaline. 32P incorporation into total phospholipids, individual phospholipids and polyphosphoinositides was analysed in whole tissue homogenates and membranes, enriched in sarcoplasmic reticulum, prepared from the same hearts. Isoprenaline stimulation of the hearts did not result in any significant changes in the levels of phosphate incorporation in the total phospholipid present in cardiac homogenates (11.6 +/- 0.4 nmol of 32P/g for control hearts and 12.4 +/- 0.5 nmol of 32P/g for isoprenaline-treated hearts; n = 6), although there was a significant increase in the degree of phospholipid phosphorylation in sarcoplasmic reticulum (3.5 +/- 0.3 nmol of 32P/mg for control hearts and 6.7 +/- 0.2 nmol of 32P/mg for isoprenaline-treated hearts; n = 6). Analysis of 32P incorporation into individual phospholipids and polyphosphoinositides revealed that isoprenaline stimulation of the hearts was associated with a 2-3-fold increase in the degree of phosphorylation of phosphatidylinositol monophosphate and bisphosphate as well as phosphatidic acid in both cardiac homogenates and sarcoplasmic reticulum membranes. In addition, there was increased phosphate incorporation into phosphatidylinositol in sarcoplasmic reticulum membranes. Thus, perfusion of guinea pig hearts with isoprenaline is associated with increased formation of polyphosphoinositides and these phospholipids may be involved, at least in part, in mediating the effects of beta-adrenergic agents in the mammalian heart.     

Effect of acute hypobaric hypoxia on 32-P incorporation into phospholipids of alveolar surfactant, lung, liver and plasma of rat.

Exposure of adult rats to hypobaric hypoxia caused hypolipidemia, hypotriglyceridemia and hypophospholipidemia. Hypobaric hypoxia produced an increase in liver triglyceride and cholesterol levels and a decrease in lung triglyceride, total phospholipid and phosphatidyl choline. The proportion of phosphatidyl choline in the pulmonary surfactant fraction I phospholipids (responsible for reducing surface tension) decreased (55.2% as compared to 80.4% in control animals). Incorporation of 32-P into liver phosphatidyl ethanolamine was significantly increased, incorporation into lung phosphatidyl choline and phosphatidyl ethanolamine was increased whereas a decreased incorporation into plasma phosphatidyl choline was observed. The data suggest an enhanced lipid synthesis in liver with a probable impairment of mobilization into plasma.     

Biochemical and Molecular Responses to Loss of Renal Mass: Membranes and Protein Synthesis: Metabolic Response to Renal Compensatory Growth

Forty-eight hours after unilateral nephrectomy in young male Sprague-Dawley rats the concentrations of free methionine, alanine and tyrosine in renal cortical tissue were increased by 15-65 percent while the corresponding plasma concentrations decreased by 23-35 percent. The renal cortical concentrations of valine and leucine increased by 41 percent and 26 percent while plasma concentrations remained unchanged. The cortical concentrations of ornithine, serine and threonine remained unchanged while the plasma concentration decreased by approximately one-third. The total free amino acid contained in the cortex was not changed, while total free amino acids in plasma decreased by 7 percent. These data are thought to reflect an increased uptake of methionine and tyrosine into renal cells during compensatory hypertrophy, and an increased incorporation into renal protein of serine, threonine and ornithine. All these changes as well as all other biochemical changes accompanying compensatory hypertrophy with the exception of an increase of the RNA/DNA ratio were prevented by starvation for 48 hours after unilateral nephrectomy.In young male Sprague-Dawley rats and adult male Charles River mice, the incorporation of ¹⁴C-choline into acid-insoluble phospholipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin) was already accelerated 5 minutes after contralateral nephrectomy and further rose to +68 ± 7 percent within 20 minutes to 3 hours. Incorporation of ¹⁴C-choline into phospholipids remained accelerated for two to three days and reflected increased rates of phospholipid synthesis rather than increased choline uptake. Three hours after unilateral nephrectomy in mice, incorporation of i.p. injected ¹⁴C-choline into phospholipids was accelerated 25 percent. The rate of turnover of free labelled renal phospholipids was not accelerated during compensatory renal growth. The very early increase of choline incorporation into phospholipids after contralateral nephrectomy, therefore, appears to reflect an increased rate of synthesis of membrane material.     

Phospholipid methylation and taurine content of synaptosomes from cerebral cortex of developing rat.

Changes in taurine concentration and rate of methylation of phosphatidylethanolamine have been examined in rat brain synaptosomes over the course of development. At 7, 14, 21, 28 and 56 days of age, rats were injected i.p. with 300 microCi/kg [3H-methyl]methionine. Synaptosomes (P2B fraction) were isolated from the cerebral cortex 9 h later and incorporation of the methionine methyl group into phospholipid and protein was investigated. Synaptosomal taurine and methionine concentrations were determined at the same ages, as were the concentrations of the major classes of phospholipids (phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine and phosphatidylserine). Methionine concentration increased between day 7 and 14 and fell thereafter. Phospholipid methylation rates calculated from the specific activity of synaptosomal methionine were high from days 7 and 14 and then fell, whereas protein methionylation increased between day 7 and 28 and then decreased. A strong correlation was found between the taurine concentration of the synaptosome and phospholipid methylation rates during brain development. Protein methionylation rates, however, showed no correlation with taurine concentration.     

Effects of dexamethasone on lipid metabolism in rat organs

Injecting of dexamethasone (10 mg/kg body weight) for 8 days to rats decreased the body weight and feed intake by 29 and 50%, respectively. The increase in weights of liver, heart, kidneys and testes per 100 g body weight was 55, 37, 33 and 13%, respectively. Though, in general, the triglyceride content increased in all the organs, maximum increase (9-fold) was observed in the liver. The plasma showed elevated levels of triglycerides, cholesterol and phospholipids. In hepatic mitochondrial membranes, the content of protein, phospholipids and cholesterol decreased/g tissue. The percent 14C distribution, as a part of total incorporation in nonpolar lipids, of [14C]acetate into triglycerides of liver, kidneys and testes increased significantly. The increased turnover of phospholipids in liver and heart was mainly due to increased turnover of phosphatidyl choline (PC) and phosphatidyl ethanolamine in liver and PC in heart. Turnover of phospholipids of testes was not affected.     

Effect of excess and deficiency of vitamin A on the utilization of FFA by liver and skeletal muscle.

Fatty acid metabolism in liver and skeletal muscle has been studied in rats treated with high doses of vitamin A and in those made vitamin A-deficient. Ingestion of 30,000 IU of vitamin A for two days resulted in increased incorporation of palmitate-1-14C into triglycerides but not into phospholipids. Accumulation of hepatic triglycerides was observed in vitamin A-fed rats. Deficiency of vitamin A did not cause any change in the triglyceride or phospholipid content of the liver. The rate of hepatic fatty acid oxidation and ketogenesis was markedly increased in vitamin A-fed rats. The experimental evidence indicated that vitamin A may have a stimulatory effect on these processes apart from that exerted by the high plasma FFA level in vitamin A-fed rats. Oxidation of palmitate-1-14C into C32 by skeletal muscle (latissimus dorsi) was also increased as a result of vitamin A administration. Vitamin A deficiency did not cause any change in fatty acid oxidation by liver and skeletal muscle. Hepatic palmitoyl-CoA synthetase activity was decreased in vitamin A-deficient rats. The results presented suggest that vitamin A may be required for the uptake and utilization of fatty acids by liver and akeletal muscle.     

Metabolism of fatty acids by bovine spermatozoa

The incorporation of (14)C-labelled myristic, palmitic, stearic, oleic and linoleic acids in vitro into the lipids of bovine spermatozoa was measured at intervals from 2min to 2h. All acids were rapidly incorporated into diglycerides, myristic acid being metabolized to the greatest extent. Whereas the low incorporation of acids into total phospholipids reflected the relative stability of the major phospholipid fractions in sperm, the minor phospholipids, particularly phosphatidylinositol, showed comparatively high metabolic activity. Although, in general, saturated acids were incorporated more actively than unsaturated substrates, stearic acid was poorly incorporated into all lipids except phosphatidylinositol. In regard to fatty acid composition of sperm lipids it was notable that diglycerides contained myristic acid as the major component, and this acid was also a prominent moiety of phosphatidylinositol. Docosahexaenoic acid was the principal fatty acid of the major phospholipid classes. These findings have been discussed in relation to the role of lipids in the metabolism of spermatozoa.     

Essential fatty acids in tissue phospholipids and triglycerides of the zinc-deficient rat

This study addressed the possibility that zinc deficiency has different effects on the fatty acid composition of triglyceride compared to total phospholipid. Male weanling Sprague-Dawley rats were maintained for 6 weeks on a semisynthetic diet deficient in zinc (3 mg/kg zinc). Control rats (40 mg/kg zinc) were pair-fed. Lipid fractionation and fatty acid analysis were by thin-layer and gas chromatography, respectively. In zinc-deficient rats, the percentage of linoleic acid was increased or that of arachidonic acid was decreased in total phospholipids of plasma, liver, and testis, and in skin total lipids. Saturated and monounsaturated fatty acids were increased in the triglyceride of liver but decreased in the triglyceride of epididymal fat of zinc deficient rats. Essential fatty acids, as a proportion of total fatty acids, were decreased in triglyceride of liver but increased in triglyceride of epididymal fat of zinc-deficient rats. Our fatty acid data from tissue total phospholipids therefore support the concept that linoleic acid desaturation is impaired in zinc deficiency.     

Effect of triiodothyronine on phospholipid metabolism in skeletal muscles of the rat.

The aim of the present study was to examine the effect of treatment with triiodothyronine (T3) on certain aspects of phospholipid metabolism in skeletal muscles. Rats were injected with triiodothyronine (T3) daily (10 microg x 100 g(-1) b.w., s.c.) for six days. Saline-treated rats served as controls. 24 h after the last dose of T3, 14C palmitic acid suspended in the serum of a donor rat, was administered intravenously. Thirty min later, samples of the soleus, white and red section of the gastrocnemius and blood from the abdominal aorta were taken. The muscle phospholipids were extracted and separated into different fractions by means of thin layer chromatography. The following fractions were obtained: shingomeylin, phosphatidylcholine phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and cardiolipin. The phospholipids were quantified and their radioactivity was measured. The plasma free fatty acid concentration and radioactivity was also determined. Treatment with T3 reduced the content of phosphatidylinositol and phosphatidylserine in each muscle type, whereas the concentration of other phospholipids remained stable. T3 increased markedly incorporation of the blood-borne fatty acids into each phospholipid fraction in the muscles. It is concluded that an excess of T3 influences the metabolism of phospholipids in skeletal muscles.     

Protein synthesis by perfused hearts from normal and insulin-deficient rats. Effect of insulin in the presence of glucose and after depletion of glucose, glucose 6-phosphate and glycogen

In the absence of glucose, insulin stimulated the incorporation of (14)C-labelled amino acids into protein by perfused rat hearts that had been previously substantially depleted of endogenous glucose, glucose 6-phosphate and glycogen by substrate-free perfusion. This stimulation was also demonstrated in hearts perfused with buffer containing 2-deoxy-d-glucose, an inhibitor of glucose utilization. It is concluded that insulin exerts an effect on protein synthesis independent of its action on glucose metabolism. Streptozotocin-induced diabetes was found to have no effect either on (14)C-labelled amino acid incorporation by the perfused heart or on the polyribosome profile and amino acid-incorporating activity of polyribosomes prepared from the non-perfused hearts of these insulin-deficient rats, which show marked abnormalities in glucose metabolism. Protein synthesis was not diminished in the perfused hearts from rats treated with anti-insulin antiserum. The significance of these findings is discussed in relation to the reported effects of insulin deficiency on protein synthesis in skeletal muscle.     

Phospholipid composition of oligodendroglial cells during normal development and in 18 day old hyperthyroid and malnourished rats.

The phospholipid composition of isolated oligodendroglial cell perikarya was studied in normal rats during development and in 18 day old malnourished and hyperthyroid rats. Phosphatidyl choline and phosphatidyl ethanolamine were found to be the major phospholipid constituents of oligodendroglial cells. Phospholipid content increased during development, mainly due to an increase of the above mentioned phospholipids. The major changes were observed in sphingomyelin, phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine between 18 and 30 days of age. The phospholipid and protein content per cell was significantly decreased in the oligodendroglial cells isolated from malnourished rats as compared to controls. When data were expressed as a function of total proteins, the composition was similar to that of normal animals. In the hyperthyroid rats on the other hand, there were no changes in the amount of phospholipids per cell, while phospholipids per milligram of total oligodendroglial cell protein were markedly decreased. The changes in myelin composition produced by hyperthyroidism that we have previously described, do not follow closely those produced by this experimental condition in oligodendroglial cells, suggesting that the metabolism of myelin might be to a certain extent, independent of that in the parent cell.     

K-FGF mediated transformation and induction of metastatic potential involves altered ornithine decarboxylase and S-adenosylmethionine decarboxylase expression – role in cellular invasion

Adult male Wistar rats were exposed to intermittent high altitude hypoxia of 7000 m simulated in a hypobaric chamber for 8 h/day, 5 days a week; the total number of exposures was 25. The concentration of individual phospholipids and their fatty acid (FA) profile was determined in right (RV) and left (LV) ventricles. Adaptation to hypoxia decreased the concentration of diphosphatidylglycerol (DPG) in hypertrophied RV by 19% and in non-hypertrophied LV by 12% in comparison with normoxic controls. Chronically hypoxic hearts exhibited lower phospholipid n-6 polyunsaturated FA (PUFA) content mainly due to decreased linoleic acid (18:2n-6), which was opposed by increased n-3 PUFA mainly due to docosahexaenoic acid (22:6n-3) in phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI). The content of arachidonic acid (20:4n-6) was unchanged in total phospholipids, but in PC it was increased in both ventricles (by 22%) and in PE decreased in LV only (by 20%). Chronic hypoxia increased the un-saturation index of PC and PE in both ventricles. The content of monounsaturated FA (MUFA) was increased and 18:2n-6 decreased in DPG. The proportion of saturated FA was increased in PC and PI of hypoxic RV but not LV. The FA composition of phosphatidylserine was not altered in hypoxic ventricles. It is concluded that chronic hypoxia led to only minor changes in individual phospholipid concentration in rat ventricular myocardium, but markedly altered their FA profile. These changes, in particular the greater incorporation of n-3 PUFA into phospholipids and increased un-saturation index, may lead to a better preservation of membrane integrity and thereby contribute to improved ischemic tolerance of chronically hypoxic hearts.     

Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function

Long-chain acyl-CoA synthetase 1 (ACSL1) contributes more than 90% of total cardiac ACSL activity, but its role in phospholipid synthesis has not been determined. Mice with an inducible knockout of ACSL1 (Acsl1^T−/−) have impaired cardiac fatty acid oxidation and rely on glucose for ATP production. Because ACSL1 exhibited a strong substrate preference for linoleate, we investigated the composition of heart phospholipids. Acsl1^T−/− hearts contained 83% less tetralinoleoyl-cardiolipin (CL), the major form present in control hearts. A stable knockdown of ACSL1 in H9c2 rat cardiomyocytes resulted in low incorporation of linoleate into CL and in diminished incorporation of palmitate and oleate into other phospholipids. Overexpression of ACSL1 in H9c2 and HEK-293 cells increased incorporation of linoleate into CL and other phospholipids. To determine whether increasing the content of linoleate in CL would improve mitochondrial respiratory function in Acsl1^T−/− hearts, control and Acsl1^T−/− mice were fed a high-linoleate diet; this diet normalized the amount of tetralinoleoyl-CL but did not improve respiratory function. Thus, ACSL1 is required for the normal composition of several phospholipid species in heart. Although ACSL1 determines the acyl-chain composition of heart CL, a high tetralinoleoyl-CL content may not be required for normal function.     

Normal Myelin Composition and Phospholipid Synthesis in Adrenalectomized Rats with Reduced Brain Myelin and Glycerol 3-Phosphate Dehydrogenase Activity

The composition of CNS myelin was investigated in rats adrenalectomized at day 14 and killed 7 days later, previously shown to result in a 25% reduction in the amount of bulk-isolated myelin and a 40% decrease in brain glycerol 3-phosphate dehydrogenase activity. The proportions of the major myelin proteins, as well as the specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, were the same in the myelin from both adrenalectomized and control animals. The amount of total phospholipid and the proportions of individual phospholipids were also normal in myelin from the adrenalectomized animals. The amount of nonmyelin phospholipid in whole brain was unchanged by adrenalectomy. Labeling studies carried out 4 days after adrenalectomy of 14-day-old animals showed no change in the synthesis rates of the major myelin phospholipids as compared with the synthesis rate of nonmyelin phospholipids. Furthermore, incorporation of [1,(3)-14C]glycerol into the glycerol moiety of ethanolamine plasmalogen, which requires glycerol 3-phosphate dehydrogenase, was also normal, showing that the reduced oligodendroglial glycerol 3-phosphate dehydrogenase activity following adrenalectomy was not rate-limiting for myelin phospholipid synthesis.     

Utilization of endogenous lipid by the isolated perfused rat heart

1. The lipids of the rat heart have been studied with regard to amount, classes present and fatty acid composition of free fatty acids, triglycerides and phospholipids. Myocardial lipid contained 300μmoles of total fatty acid/g. dry wt. of which only 2–4μmoles were free; the remainder was esterified, chiefly as phospholipid. Neutral esters, of which triglyceride was the principal form, made up 15% of the total fatty acids. 2. When normal hearts were perfused with a nutrient-free medium until exhaustion, the triglyceride concentration declined from 43 to 13μmoles/g. dry wt. The content of phospholipids, partial glycerides and cholesteryl esters did not change. When the lipids of the rat heart were labelled with [1-¹⁴C]palmitate before perfusion with non-nutrient medium, radioactivity disappeared from the triglyceride, diglyceride and free fatty acid fractions, but not from the phospholipid or other ester classes. 3. These experiments support the view that only a small fraction of the total cardiac lipid, principally triglycerides and to a smaller extent diglycerides, is available as a source of fuel in the absence of exogenous substrate.     

Influence of aminophylline on the lipids in Microsporum gypseum.

The effect of aminophylline on the lipid synthesis of Microsporum gypseum has been examined. A decreased incorporation of [14C]acetate into lipids was observed when the cells were incubated for 1 h with aminophylline which was reflected in all the individual lipid fractions. However, cells grown with aminophylline in the growth medium exhibited increased levels of total phospholipids, which was probably due to a rise in intracellular cAMP as these cells exhibited 4-fold increased levels of cAMP. Decreased activity of phosphodiesterase by aminophylline accounts for the increased cAMP levels. Increased phospholipid content in aminophylline grown cells was further supported by the increased incorporation of [14C]acetate into phospholipids as well as increased activities of phospholipid biosynthetic enzymes in comparison to non-supplemented cells.     

Use of the isolated perfused rat lung in studies on lung lipid metabolism

A procedure for the use of the isolated perfused rat lung in studies on metabolic regulation has been developed. The procedure, reasonably uncomplicated, yet physiological, maintains the lung so that edema is not observed. The phospholipid content remains normal, and incorporation of [1-(14)C]-palmitate, [2-(14)C]acetate, and [U-(14)C]glucose is linear with time for a minimum of 2 hr. The incorporation of [1-(14)C]-palmitate and [2-(14)C]acetate into the total lung phospholipid fraction and into the phosphatidylcholine and phospatidylethanolamine fractions has been studied. Increasing the concentration of palmitate in the medium from 0.14 to 0.51 mm increased by 60% the incorporation of [1-(14)C]palmitate into the total lung phospholipid fraction at 2 hr. When the palmitate concentration of the medium was 0.14 mm, addition of 0.11 and 0.79 mm oleate to the medium decreased [1-(14)C]palmitate incorporation into the total lung phospholipid fraction at 2 hr by 37 and 49%, respectively. The results suggest that the incorporation of exogenous fatty acids, present in the medium perfusing the lung, into lung phospholipids may depend upon the fatty acid composition of the medium. Known specific acyltransferase activities may be responsible for the ordered incorporation of available fatty acids into lung phospholipids.     

Phenobarbital-induced alterations in phosphatidylcholine and triglyceride synthesis in hepatic endoplasmic reticulum

Biosynthetic pathways of phosphatidylcholine and triglyceride were studied in proliferating hepatic endoplasmic reticulum of rats pretreated with phenobarbital. Phosphatidylcholine accounted for the major increment in membrane phospholipid. In vitro measurements of hepatic microsomal enzymes which catalyze phosphatidylcholine biosynthesis revealed a significant increase in specific activity of the enzyme governing phosphatidylcholine synthesis by sequential methylation of phosphatidylethanolamine. The specific activity of phosphorylcholine-glyceride transferase, which catalyzes phosphatidylcholine synthesis from d-1,2-diglyceride and CDP-choline, was not altered. Specific activity of diglyceride acyltransferase, which catalyzes triglyceride biosynthesis, was increased to a degree comparable to the increase in specific activity found in the phenobarbital-induced drug-metabolizing enzyme which oxidatively demethylates aminopyrine. In vivo incorporation of methyl-(3)H from l-methionine-methyl-(3)H into microsomal phosphatidylcholine was significantly increased, resulting in an increased methyl-(3)H to choline-1,2-(14)C incorporation ratio of more than three times that found in control animals. A comparable increase in this incorporation ratio was noted in serum phospholipids. The in vitro enzyme studies, in agreement with in vivo incorporation data, indicate that the increase in phosphatidylcholine content of phenobarbital-induced proliferating endoplasmic reticulum is related to increased activity of the pathway of phosphatidylcholine biosynthesis involving the sequential methylation of phosphatidylethanolamine.     

Stimulation of surfactant phospholipid biosynthesis in the lungs of rats treated with silica.

The effects of intratracheally instilled silica (10 mg/rat) on the biosynthesis of surfactant phospholipids was investigated in the lungs of rats. The sizes of the intracellular and extracellular pools of surfactant phospholipids were measured 7, 14 and 28 days after silica exposure. The ability of lung slices to incorporate [14C]choline and [3H]palmitate into surfactant phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) was also investigated. Both intra- and extra-cellular pools of surfactant phospholipids were increased by silica treatment. The intracellular pool increased linearly over the 28-day time period, ultimately reaching a size 62-fold greater than controls. The extracellular pool also increased, but showed a pattern different from that of the intracellular pool. The extracellular pool increased non-linearly up to 14 days, and then declined. At its maximum, the extracellular pool was increased 16-fold over the control. The ability of lung slices to incorporate phospholipid precursors into surfactant-associated PC and DSPC was elevated at all time periods. The rate of incorporation of [14C]choline into surfactant PC and DSPC was maximal at 14 days and was nearly 3-fold greater than the rate in controls. The rate of incorporation of [3H]palmitate was also maximal at 14 days, approx. 5-fold above controls for PC and 3-fold for DSPC. At this same time point, the microsomal activity of cholinephosphate cytidylyltransferase was increased 4.5-fold above controls, but cytosolic activity was not significantly affected by silica treatment. These data indicate that biosynthesis of surfactant PC is elevated after treatment of lungs with silica and that this increased biosynthesis probably underlies the expansion of the intra- and extra-cellular pools of surfactant phospholipids.