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Biomedical subjects

G Dallner

Publications and source records attributed to G Dallner.

230 records · Page 13Linked to original sources
PubMed1968

Lipid composition and turnover of rough and smooth microsomal membranes in rat liver.

Subfractions of rat liver microsomes (rough, smooth I, and smooth II), isolated in a cation-containing sucrose gradient system, were analyzed. After removal of adsorbed and luminal protein, these subfractions had the same phospholipid/protein ratio, about 0.40. Both the classes and the relative amounts of phospholipids were similar in the three subfractions, but the relative amounts of neutral lipids (predominantly free cholesterol and triglycerides) were higher in smooth I and especially in smooth II than in rough microsomes. Various pieces of evidence indicate that the neutral lipids are tightly bound to the membranes. Glycerol-(3)H was incorporated into the phospholipids of the rough and smooth I microsomes significantly faster than into those of the smooth II membranes; (32)P incorporation followed a similar but less pronounced pattern. Acetate-(3)H was incorporated into the free cholesterol of smooth I microsomes only half as fast as into the other two subfractions. Injection of phenobarbital increased the cellular phospholipid and neutral lipid content in the rough and smooth I, but not in the smooth II microsomes. Consequently, the neutral lipid/phospholipid ratio of all three subfractions remained unchanged after phenobarbital treatment. It is concluded that the membranes of the rough and the two smooth microsomal subfractions from rat liver have a similar phospholipid composition, but are dissimilar in their neutral lipid content and in the incorporation rate of precursors into membrane lipids.

Acetates↗
PubMed1966

Biogenesis of endoplasmic reticulum membranes. I. Structural and chemical differentiation in developing rat hepatocyte.

The development of the endoplasmic reticulum of rat hepatocytes was studied during a period of rapid cell differentiation, i.e., from 3 days before to 8 days after birth. Before birth, the ER increases in volume, remaining predominantly rough surfaced; after birth, the increase continues but affects mainly the smooth-surfaced part of the system. These changes are reflected in variations of the RNA/protein and PLP/protein ratios of microsomal fractions: the first decreases, while the second increases, with age. The analysis of microsomal membranes and of microsomal lipids indicates that the PLP/protein ratio, the distribution of phospholipids, and the rate of P(32) incorporation into these phospholipids show little variation over the period examined and are comparable to values found in adult liver. Fatty acid composition of total phosphatides undergoes, however, drastic changes after birth. During the period of rapid ER development in vivo incorporation of leucine-C(14) and glycerol-C(14) into the proteins and lipids of microsomal membranes is higher in the rough-than in the smooth-surfaced microsomes, for the first hours after the injection of the label; later on ( approximately 10 hr) the situation is reversed. These results strongly suggest that new membrane is synthesized in the rough ER and subsequently transferred to the smooth ER.

Animals↗
PubMed1966

Biogenesis of endoplasmic reticulum membranes. II. Synthesis of constitutive microsomal enzymes in developing rat hepatocyte.

The constitutive enzymes of microsomal membranes were investigated during a period of rapid ER development (from 3 days before to 8 days after birth) in rat hepatocytes. The activities studied (electron transport enzymes and phosphatases) appear at different times and increase at different rates. The increase in the enzyme activities tested was inhibited by Actinomycin D and puromycin. G-6-Pase and NADPH-cytochrome c reductase activities appeared first in the rough microsomes, and subsequently in smooth microsomes, eventually reaching a uniform concentration as in adult liver. The evidence suggests that the enzymes are synthesized in the rough part, then transferred to the smooth part, of the ER. Changes in the fat supplement of the maternal diet brought about changes in the fatty acid composition of microsomal phospholipids but did not influence the enzymic pattern of the suckling. Microsomes from 8-day-old and adult rats lose 95% of PLP and 80% of NADH-cytochrome c reductase activity after acetone-H(2)O (10:1) extraction. However, one-half the original activity could be regained by adding back phospholipid micelles prepared from purified phospholipid, or from lipid extracts of heart mitochondria, or of liver microsomes of 8-day or adult rats, thus demonstrating an activation of the enzyme by nonspecific phospholipid. The results suggest that during development the enzymic pattern is not influenced by the fatty acid or phospholipid composition of ER membranes.

Animals↗
PubMed1966

Mechanism of the cation effect in subfractionation of microsomes.

It was previously found that cations introduced into a discontinuous sucrose gradient exert a very pronounced effect on microsomal vesicles, and this principle proved to be effective in microsomal subfractionation. The mechanism of the cation effect was investigated. By using the radioactive isotopes (137)Cs and (85)Sr, it could be calculated that the amount of ions bound to the various subfractions increases their density by 0.14%, thereby enhancing the sedimentation velocity by only approximately 7%. In the presence of Cs(+) the total volume of the microsomal pellet was decreased by approximately 15%. Assuming this change in volume to be due to a contraction of the individual vesicles, a roughly 2(1/2)-fold increase in sedimentation velocity would be expected. It is further demonstrated, on the basis of light scattering and millipore filtration experiments, that monovalent cations cause an extensive aggregation of rough microsomes and a less pronounced aggregation of smooth microsomes. The mean radius of the sedimenting particles of rough microsomes was found to be at least doubled or trebled in the presence of Cs(+), which would give a 4- to 9-fold increase in the sedimentation velocity. Aggregation, therefore, appears to be the main factor in the accelerated sedimentation of rough microsomes in the presence of CsCl. Divalent cations exert a similar effect on a subfraction of the smooth microsomes. Isolated smooth microsomes are very unstable and often exhibit spontaneous aggregation. The presence of attached ribosomes, however, appears to impart greater stability to the rough microsomes as well as increasing their ability to bind monovalent cations. The primary cause of the aggregation of microsomal vesicles is probably due to a change in net charge.

Adenosine Triphosphatases↗
PubMedDate not supplied

Phthalate esters and their effect on the liver.

The advantageous properties of polyvinyl chloride plastics make these materials indispensable at all levels of human life, and there is no reason to believe that the upward trend of their use will change. One third of most polyvinyl chloride plastics consists of plasticizers, mostly phthalate esters, which may migrate out contaminating our environment and consequently our bodies. Experimental results indicate that chronic exposure to phthalic esters may be responsible for a number of adverse health effects. Phthalates change the structure and function of the liver in a profound manner by inducing peroxisomes, mitochondria and enzymes which participate in fatty acid transport and beta-oxidation. Prolonged administration of phthalate esters, in doses comparable to those occurring in human exposures, seems to have an accumulative effect on the liver. Liver biopsies taken from dialysis patients show peroxisome proliferation which again warn of the possibility that human health may be influenced by plasticizers.

Acyl-CoA Dehydrogenase↗
PubMedDate not supplied

Glutathione transferase alpha as a marker for tubular damage after trichloroethylene exposure.

To investigate possible persistent nephrotoxic effects of trichloroethylene (TRI), a retrospective study was carried out on 39 workers exposed to high levels of TRI from 1956 to 1975. Total protein levels in urine, as well as serum and urine creatinine and serum urea were unchanged in comparison with the control. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was applied to differentiate between tubular and/or glomerular dysfunction. Urinary excretion of alpha-1-microglobulin and glutathione transferase (GST) alpha, as markers of proximal tubular damage, were correlated with the SDS-PAGE patterns of urinary proteins both in the TRI exposed and the control group. GST alpha was found in elevated concentrations in the urine of the TRI-exposed workers. No increase of urinary GST alpha was observed in the control group, even when alpha-1-microglobulin was elevated as a result of non-toxic damage. Both in the control and exposed groups, GST pi, a marker of distal tubular damage, was in the normal range. The results show that chronic exposure to high doses of TRI causes persistent changes to the proximal tubular system of the kidney and that GST alpha excretion into the urine is a marker well suited for quantitation of the extent of renal damage.

Biomarkers↗
PubMedDate not supplied

The lipid compositions of different regions of rat brain during development and aging.

The lipid contents in different regions of the rat brain were analyzed from birth to the age of 2 years. The total brain phospholipid content increased threefold during the first 20 postnatal days. The cholesterol content elevated extensively during the first 2 months of life and, after this period, remained unchanged. The level of dolichol increased almost 100-fold during the first 10 months of life and continued to increase thereafter. Some modifications in the dolichol isoprenoid pattern were also observed. An increase in the brain ubiquinone level occurred during the first few months of life, but no further change was observed after this period. Ubiquinone-9 and -10 constituted 70 and 30%, respectively, of the total ubiquinone in all regions and all subcellular fractions. The alpha-tocopherol content increased during the first 3 weeks of life and was unchanged thereafter. These results demonstrate characteristic changes in the lipid contents of various regions of rat brain during development and aging.

Aging↗
PubMedDate not supplied

Influence of chronic fluorosis on membrane lipids in rat brain.

Brain membrane lipid in rats were analyzed after being fed either 30 or 100 ppm fluoride for 3, 5, and 7 months. The protein content of brain with fluorosis decreased, whereas the DNA content remained stable during the entire period of investigation. After 7 months of fluoride treatment, the total brain phospholipid content decreased by 10% and 20% in the 30 and 100 ppm fluoride groups, respectively. The main species of phospholipid influenced by fluorosis were phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine. The fatty acid and aldehyde compositions of individual phospholipid classes were unchanged. No modifications could be detected in the amounts of cholesterol and dolichol. After 3 months of fluoride treatment, ubiquinone contents in brain were lower; however, at 7 months they were obviously increased in both groups of fluoride treatment. The results demonstrate that the contents of phospholipid and ubiquinone are modified in brains affected by chronic fluorosis and these changes of membrane lipids could be involved in the pathogenesis of this disease.

Animals↗
PubMedDate not supplied

Immunohistochemical localization of alpha and pi class glutathione transferases in normal human tissues.

The distribution of alpha and pi class glutathione transferases in autopsy and biopsy samples of normal human tissues was investigated by immunohistochemistry. The class alpha glutathione transferases exhibited restricted distribution. Intensive staining was visible in all hepatocytes, in kidney proximal tubular cells, in the zona reticularis of adrenal cortex and in Leydig cells of testis. Staining of lesser intensity could also be observed in the gastrointestinal epithelium, exocrine pancreas and some bile and pancreas ducts. In colon and gall bladder only nuclei were stained, but in the other tissues both nuclei and cytoplasm contained alpha class glutathione transferases. Glutathione transferase pi exhibited a more general distribution and could be observed in epithelia of the respiratory, gastrointestinal and urinary tracts, in all endocrine cells investigated, and also in the exocrine glands of prostate, in smooth muscle, adipocytes, blood vessel endothelium and placenta. It was also visible in the Schwann cells of peripheral nerves and in the choroid plexus. In gall bladder and colon only nuclei were stained, while in the intrahepatic bile ducts only cytoplasm was stained. All other positive cells exhibited glutathione transferase pi in both nuclei and cytoplasm.

Animals↗