dolichols and Body-Weight

Previous investigations have demonstrated that 1,2-dichloroethane (DCE) poisoning affects dolichol (Dol) concentration in rat liver. Dol, a long-chain polyprenol, is considered an important membrane component: as dolichyl phosphate, it is rate limiting for the synthesis of glycoprotein; as free or fatty acid, it is highly concentrated in the Golgi apparatus (GA) where it can increase membrane fluidity and permeability, required glycoprotein maturation and secretion. DCE biotransformation may stimulate pro-oxidant events through hepatocellular glutathione depletion. Since the molecules of Dol are susceptible to oxidative degradation, the aim of this investigation is to verify whether vitamin E (vit. E) supplementation in rats is able to prevent Dol breakdown during acute DCE treatment. Before acute DCE administration (628 mg/kg body weight), a group of male Wistar rats were pretreated with vit. E (33 mg/kg body weight) for 3 days. High-performance liquid chromatography analysis has shown that within 5-60 min after DCE administration, the Dol concentration decreased in liver homogenate, cytosol, microsomes and GA. Particularly, 60 min after the treatment, Dol levels in the trans Golgi fraction were 71% lower than in controls. Rat pre-treatment with vit. E prevented the DCE-induced decrease in Dol concentrations of all liver fractions considered, in particular the reduction of total-Dol observed in the trans Golgi fraction 60 min after treatment was only 40%. These data suggest that hepatic metabolism of DCE is able to promote peroxidative attacks which lead to the degradation of Dol molecules. The pre-treatment of rats with vit. E results in a good, although not complete, prevention of total-Dol depletion after DCE poisoning.

Topics: Animals; Ascorbic Acid; Body Weight; Chromatography, High Pressure Liquid; Dolichols; Ethylene Dichlorides; Golgi Apparatus; Iron; Lipid Peroxidation; Liver; Male; Oxidants; Rats; Rats, Wistar; Subcellular Fractions; Vitamin E

A diet containing 15% (w/w) fat and 20% (w/w) of either casein or soy protein was fed to rats between 1 and 18 months of age. The effects of these dietary proteins on the accumulation of cholesterol and dolichols in kidney, spleen, brain, and heart were studied. The amount of cholesterol in these tissues was not influenced by the diet. In kidney and spleen, the amount of dolichols in rats fed the experimental diets was 50-70% higher than those in rats fed the lab chow diet. The contents of spleen dolichols in rats fed the soy protein diet tended to be higher than those in rats fed the casein diet. The amount of dolichols in heart and brain was not influenced by the diet. The proportion of spleen dolichyl fatty ester in rats fed the experimental diets was higher than that in rats fed the lab chow. The distribution of the dolichol isoprenologues was not influenced by the diet. There was a shift in the dolichol isoprenologues in kidney and spleen toward ones of lower chain length until 2 months of age, and after that there was no change. However, in heart and brain they shifted toward ones of lower chain length with aging. Our results suggested that dolichol metabolism may be influenced by fat content in the diets and differed among rat tissues.

Topics: Aging; Animals; Body Weight; Brain; Caseins; Cholesterol; Dietary Fats; Dietary Proteins; Dolichols; Esters; Fatty Acids; Heart; Kidney; Male; Myocardium; Organ Size; Organ Specificity; Rats; Rats, Wistar; Soybean Proteins; Spleen

A diet containing 15% (w/w) fat and 20% (w/w) of either casein (CAS) or soy protein (SOY) was fed to 4-week-old rats for a period of 18 months. The effects of these dietary proteins on the accumulation of cholesterol and dolichol in livers were studied. After 1 month, the amount of liver cholesterol was about 5 mg/g of liver. After an additional 5 months of feeding, there was a slight decrease in cholesterol per gram of liver (3.6 mg/g of liver in CAS-fed rats and 2.6 mg/g of liver in SOY-fed rats). However, after 18 months, there were a remarkable increase (7.5 mg/g of liver) in CAS-fed rats and only a slight increase in SOY-fed rats. The proportions of liver cholesterol ester in rats fed the CAS diet were 60-70% of the total cholesterol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 70%, of cholesterol ester. The amounts of liver dolichol in rats fed the CAS and SOY diets after feeding for 18 months were 60 micrograms and 47 micrograms of liver, respectively. There was a 1.5-fold increase in both diets for a period of 18 months. The proportions of liver dolichyl fatty ester in rats fed the CAS diet were 35-40% of the total dolichol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 36%, of dolichyl fatty ester. The proportions of dolichol ester in rats fed the SOY diet were 25-30% after 6 and 18 months of feeding. These observations indicated that the SOY diet depresses the accumulation of both liver dolichol and cholesterol.

Topics: Animals; Body Weight; Caseins; Cholesterol; Cholesterol Esters; Dietary Proteins; Dolichols; Glycine max; Liver; Male; Organ Size; Plant Proteins, Dietary; Rats; Rats, Wistar; Soybean Proteins; Time Factors

The concentrations of the three major cellular forms of dolichol (free, esterified and phosphorylated) were determined in murine liver, kidney and heart. The tissue levels of these forms of dolichol were studied in detail as a function of age. Changes in the activities of dolichyl phosphate phosphatase and dolichol kinase were also determined. In liver, the concentration of unesterified dolichol, fatty acyl dolichol and dolichyl phosphate increased markedly over a period of 6 to 25 months (four-fold, 5.5-fold and nine-fold, respectively). In kidney only, free dolichol and phosphorylated dolichol increased (approximately four-fold in each case). However, this tissue consistently showed the highest concentrations of all forms of dolichol as compared to liver and heart. In heart, both free and esterified dolichol concentrations increased (approximately 3.25-fold in each case); dolichyl phosphate levels were not determined in this tissue. In all tissues studied, the activity of the dolichyl phosphate phosphatase enzyme was considerably higher than that of the dolichol kinase enzyme. In liver, there was no evidence to suggest that either enzyme was critical in determining the relative concentrations of dolichol and dolichyl phosphate. Evidence for such a role for the kinase in the kidney was stronger. Treatment of aging mice with meclofenoxate, a drug that is reported to cause dissolution of lipofuscin, failed to prevent accumulation of dolichol and dolichyl phosphate with age. These observations suggest that not all accumulated dolichol is associated with lipofuscin. Meclofenoxate treatment had no consistent effect on the activities of the enzymes studied.

Topics: Aging; Animals; Body Weight; Dolichol Phosphates; Dolichols; Female; Heart; Kidney; Lipofuscin; Liver; Male; Meclofenoxate; Mice; Myocardium; Organ Size; Phosphoric Monoester Hydrolases; Phosphotransferases; Phosphotransferases (Alcohol Group Acceptor)

Previous studies in young normal rats have shown that intracerebral administration of the proteinase inhibitor, leupeptin, caused a rapid accumulation of lipofuscin-like pigment in lysosomes of brain cells (Ivy et al., 1984a). On the other hand, we have recently found that the administration of lovastatin, an inhibitor of HMG-CoA reductase, reduced the ceroid-like pigment and dolichol contents in the crushed epididymal fat pad of rats (Porta et al., 1988). In order to study now the possible modulating effects of these enzyme inhibitors on ceroidogenesis associated with vitamin E deficiency, two main groups of weanling Wistar female rats were respectively fed ad libitum a vitamin E-deficient basal diet, or the same diet supplemented with 16 mg% of dl-alpha-tocopherol acetate. The vitamin E-deficient and -supplemented rats were further subdivided and received for 8 weeks their diets alone or with 2, 1, or 0.5 g of lovastatin/kg of diet. Other subgroups were treated with constant peritoneal infusion of 0.5 mg/day of leupeptin by means of osmotic minipumps (Alzet 2002) consecutively implanted at days 15, 30, and 45. Lovastatin treatment to vitamin E-deficient rats was associated with dose-dependent toxicity, resulting in 100%, 75%, and 50% mortality at concentrations of 2, 1, and 0.5 g/kg diet, respectively. This mortality was mainly due to extensive hepatic necrosis. Food intake and growth rates were reduced, while the relative weights of liver, kidneys, spleen, heart and brain, as well as the serum levels of GPT and GOT were significantly increased over the values of the untreated vitamin E-deficient control rats. The volumetric densities of ceroid pigment and the dolichol contents in liver and kidneys were not significantly modified. Lovastatin toxicity was partially prevented by vitamin E supplementation. However, in these supplemented rats, lovastatin treatment did not modify the volumetric densities of hepatic and renal ceroid, although the contents of hepatic and renal dolichol were significantly increased. No correlations could be found between levels of hepatic or renal ceroid and total dolichol content in vitamin E-deficient and supplemented rats. Leupeptin treatment to vitamin E-deficient rats only slightly reduced food intake and growth rates, and did not significantly modify the relative organ weights or the serum levels of cholesterol, GOT and GPT. Although in both vitamin E-deficient and -supplemented rats the leupeptin treatment consistently s

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Ceroid; Cholesterol; Dolichols; Eating; Female; Kidney; Leupeptins; Liver; Lovastatin; Organ Size; Rats; Rats, Inbred Strains; Vitamin E; Vitamin E Deficiency

In order to gain information on the metabolism of dolichol, the rates of excretion of dolichol and dolichyl phosphate were determined in rats maintained on a dolichol-free diet for 10 days. Analysis of fecal samples collected every 48 h yielded mean output values of 9.0 +/- 1.4 and 20.7 +/- 3.0 micrograms/rat/day of dolichol and dolichyl phosphate, respectively. Urinary output rates were 0.56 +/- 0.12 and 0.50 +/- 0.28 microgram/rat/day of dolichol and dolichyl phosphate, respectively. Thus, excretion is one fate of endogenously synthesized dolichol compounds in the rat.

Topics: Animals; Body Weight; Chromatography, High Pressure Liquid; Diterpenes; Dolichol Phosphates; Dolichols; Feces; Liver; Male; Polyisoprenyl Phosphates; Rats; Rats, Inbred Strains; Tritium