共查询到20条相似文献,搜索用时 31 毫秒
1.
BACKGROUND: There is a major need for a mouse model of Gaucher disease, but the glucocerebrosidase knockout mouse is not viable; it dies shortly before or immediately after birth, apparently because of involvement of the central nervous system and/or skin. The most common form of Gaucher disease, type I, has a phenotype that is limited to the monocyte-macrophage system. MATERIALS AND METHODS: We have created a chimeric mouse by infusing hematopoietic stem cells from fetuses that are homozygous for the glucocerebrosidase knockout into irradiated mice. RESULTS: The chimeric mice manifested a severe deficiency of glucocerebrosidase activity in peripheral blood cells and spleen indicating a lack of cell-cell correction. Levels of glucocerebroside in spleen and liver are increased, and infusing the mice with exogenous glucocerebroside/albumin particles produced a marked increase in the amount of glucocerebroside stored in liver and spleen. Morphologically identifiable Gaucher cells were not present. CONCLUSIONS: The chimeric model reflects the increased glycolipid storage in the reticuloendothelial system that is characteristic of Gaucher disease, and could be useful as a model for studying treatment of Gaucher disease. 相似文献
2.
Characteristic distribution of glycolipids in gadoid fish nerve tissues and its bearing on phylogeny. 总被引:1,自引:0,他引:1
Glycolipids were isolated from nerve tissues of gadoid fishes including Alaskan pollack and Pacific cod. Their chemical structures were determined by gas-liquid chromatography and gas chromatography-mass spectrometry, and their constituents were analyzed in detail and compared with those of glycolipids from other fish groups. The results revealed that gadoid fish nerve membranes contain peculiar glycolipid molecular species that are distinctly different from those in other teleostean fishes and higher vertebrates. The mole percentage ratio of the four major glycolipids (cerebroside-sulfatide-galactosylglyceride-sulfogalactosylglyce ride) was 48:12:25:15, indicating profound accumulation of glycoglycerolipids. Galactosylglyceride and sulfogalactosylglyceride were primarily of the diacyl type (greater than 90%), the major fatty acids being 16:0 and 18:1. An abundance of glucocerebroside (25 to 55% of cerebroside) and its fatty acid ester (37 to 47% of ester cerebroside) was noted. Cerebroside and sulfatide were characterized by the absence of hydroxy and odd numbered fatty acids, and 24:1 acid was a predominant component of both glucocerebroside and galactocerebroside. Subcellular fractionation revealed that myelin membranes comprised such unusual glycolipid constituents as those seen in whole nerve tissues. A vertebrate whose nerve membranes consist of such peculiar glycolipid molecules has not previously been reported. The characteristics of the glycolipid composition in gadoid fishes are discussed in relation to myelin functions, physicochemical properties of nerve membranes, and the phylogenic significance of this fish group. 相似文献
3.
Kurt R. Brunden Rosilyn Gregory Jun E. Yoshino Jeffrey K. Yao 《Neurochemical research》1994,19(10):1277-1281
Schwann cells that are deprived of axonal contact switch their glycolipid metabolic pathway from primarily galactocerebroside (GalCe) synthesis to the formation of glucocerebroside (GlcCe) and its homologs. The removal of axonal influence has a dual effect on Schwann cell phenotype; they lose the ability to assemble both myelin and basement membrane. To determine whether a loss of basement membrane directly affects glycolipid expression, we have examined lipid biosynthesis in Schwann cells which were allowed to interact with axons of dorsal root ganglion neurons but which were deprived of the ability to assemble basal lamina. These Schwann cells resemble those from myelinating nerve in that they synthesize a large amount of galactohydroxycerebroside. This suggests that axon contact, even in the absence of basement membrane, is sufficient to induce the GalCe metabolic pathway.Abbreviations DRG
dorsal root ganglia
- GalCe
galactocerebroside
- GalCe-OH
galactohydroxycerebroside
- GlcCe
glucocerebroside
- GL-2
lactosylceramide
- GL-3
trihexosylceramide
- GL-4
tetrahexosylceramide
- HPTLC
high-performance thin-layer chromatography
- MGDG
monogalactosyl diacylglycerol
- NL
non-polar lipids
- PC
phosphatidylcholine
- Su
sulfatide
- Su-OH
hydroxysulfatide 相似文献
4.
Alexandre E Cahn M Abadie-Viollon C Meyer N Heyd B Mantion G Cinqualbre J David P Jaeck D Richert L 《Cell and tissue banking》2002,3(4):223-233
The aim of the present study was to analyse, retrospectively on a large panel of patients (149), the influence of the donor
liver characteristics on the outcome of human hepatocyte isolation obtained from resected liver biopsies from surgical waste
after hepatectomy. Among the pre-operative parameters, the type of disease, age and sex of the patient, previous chemotherapy,
alcohol or tobacco consumption did not affect the yield, viability, attachment rate and function of the isolated human hepatocytes.
Pre-operative biological and anatomopathological data indicated that, while mild steatosis (≤10% steatotic hepatocytes) did
also not affect the outcome of hepatocyte isolation, stronger steatosis (>10% steatotic hepatocytes) tended to decrease hepatocyte
yield. Cholestasis, as assessed by γ-glutamyl transferase serum values, significantly negatively correlated with the percentage
of digested liver and the yield of viable cells. Intra-operative clamping time, that is, warm ischaemia, longer than 30 min
was found to decrease both the percentage of digested liver and cell yield. Among the post-operative parameters, the percentage
of digested liver decreased when biopsy weights were higher than 100 g, the use of glue tended to increase both the percentage
of digested tissue and the yield of viable cells.
In conclusion, human diseased livers appear to be a valuable source of isolated functional human hepatocytes. We recommend,
for an optimal isolation, to use liver biopsies weighing less than 100 g, to glue the section surfaces of the biopsies and
to avoid the use of moderate steatotic livers (>10% steatotic hepatocytes) and cholestatic livers, as well as livers undergoing
warm ischaemia or clamping during resection due to the decrease in cell yield.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
5.
Livers from normally fed male and female rats were perfused in vitro with different amounts of oleate, and the production and properties of the very low density lipoprotein (VLDL) were studied. The mobility of the VLDL in the zonal ultracentrifuge was dependent on the uptake of free fatty acid and on the sex of the animal from which the liver was obtained. A higher proportion of the VLDL secreted by livers from females displayed a more rapid mobility in the zonal ultracentrifuge and, in addition, contained less phospholipid and cholesterol per mole triglyceride than the VLDL from the male, suggestive of larger size of the VLDL secreted by livers from the female rats. Such differences were diminished when the VLDL was compared at equal output of triglyceride but unequal uptake of free fatty acid. These data suggest that the properties of the VLDL are only secondarily modulated by sex, and primarily result from differences in the capacities of livers from either male or female rats to synthesize triglyceride for transport as VLDL. The quantity of triglyceride secreted, regardless of sex, may be an important determinant of both size and number of the VLDL particles. The incorporation of endogenous hepatic fatty acid into VLDL triglyceride was diminished in livers from both sexes by increased uptake of oleate. The greater output of VLDL triglyceride by livers from female animals was dependent on both exogenous and endogenous fatty acids when relatively small quantities of exogenous oleate were available for uptake by the liver. The proportion of palmitate and oleate in the phospholipid of the VLDL secreted by livers from male rats decreased and the content of arachidonate increased with increasing uptake of oleate; no differences were observed in the composition of the phospholipid fatty acids among the various experimental female groups, although these contained more stearate and less oleate and linoleate compared to the male groups. The change of fatty acid composition of the VLDL phospholipid may reflect inclusion of specific types of phospholipid in the VLDL structure for transport of triglyceride from the liver under particular conditions. 相似文献
6.
Thermotropic behavior of monoglucocerebroside--dipalmitoylphosphatidylcholine multilamellar liposomes 总被引:1,自引:0,他引:1
The thermotropic behavior of multilamellar liposomes prepared from mixtures of glucocerebroside and dipalmitoylphosphatidylcholine has been studied by high-sensitivity scanning calorimetry. It is shown that glucocerebroside has a marked effect on the gel--liquid crystalline transition of dipalmitoylphosphatidylcholine. The pretransition seen in pure samples of dipalmitoylphosphatidylcholine is undetectable at small mode fractions of glucocerebrosides (less than 10%). The main transition is shifted to higher temperatures and becomes broader and less cooperative in the presence of glucocerebroside. The enthalpy change of the main transition decreases with increasing the glucocerebroside content. However, this decrease is not linear with the glucocerebroside/phospholipid mole ratio. Glucocerebroside itself does not show a separate transition in the temperature range of these studies (10--75 degree C). The origin of these effects and their dependence on the glucocerebroside content suggest that the in-plane distribution of glucocerebroside molecules is affected by the physical state of the lipid bilayer and by the glucocerebroside/phospholipid mole ratio. 相似文献
7.
S P Peters L Aquino W F Naccarato J R Gilbertson W F Diven R H Glew 《Biochimica et biophysica acta》1979,575(1):27-36
The deficiency of oleic acid as one of the fatty acids in glucocerebrosides that accumulate (31--77 mg/g dry weight) in the spleen in patients with Gaucher's disease was confirmed in 9 cases. In an effort to account for the 10-fold difference between the oleoyl glycocerebroside content of glucocerebrosides in spleen from controls and patients with Gaucher's disease, we compared the ability of extracts of spleen and fibroblasts from individuals with various forms of Gaucher's disease and controls to hydrolyze [14C]stearoyl and [3H]oleoyl glucocerebroside. The residual glucosylceramidase activity in patients with Gaucher's disease hydrolyzes the glucose moiety of oleoyl glucocerebroside at approximately the same rate as that of stearoyl glucocerebroside. Similarly, the more active glucosylceramidase of control tissue acts upon both oleoyl and stearoyl glucocerebrosides with equal efficiency. These observations indicate that a mutation affecting the substrate specificity of glucosylceramidase cannot account for the lack of oleic acid-containing glucocerebrosides in patients with Gaucher's disease. Thus, the hypothesis that the difference in fatty acid composition found in glucocerebroside is obtained as a result of a mutation affecting the specificity of the residual glucosylceramidase must be rejected. 相似文献
8.
Quantitation of fibrosis in liver biopsies 总被引:3,自引:0,他引:3
C A Rubio A Porwit 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》1988,10(2):107-109
After 15 years of subjectively estimating the degree of fibrosis in liver biopsies stained with Sirius red F3BA, the amounts of Sirius red-stained fibrotic areas were quantitated with the help of a Cortex IQ 130 image quantifier. The percentage of Sirius red-stained areas was lowest in normal livers, increasing significantly in fatty livers, with stepwise higher values in chronic persistent hepatitis, toxic damage, chronic active hepatitis, fatty livers with obvious fibrosis, biliary cirrhosis and portal cirrhosis. Cases of portal cirrhosis had tenfold higher values than did normal livers. The results indicate that Sirius red is a reliable histochemical stain that can be used to quantitatively demonstrate the various degrees of fibrosis in liver biopsies. 相似文献
9.
Donated human liver in the form of precision-cut tissue slices or isolated hepatocytes, is increasingly being used to predict
metabolism and toxicity of xenobiotics in man. These tissue slices or hepatocytes can also be cold-preserved and cryopreserved
to prolong their use for biological experiments. The viability of human liver could substantially affect the outcome of such
experimentation. The goal of this investigation was to assess the viability of donated human livers, in the form of tissue
slices, as they were received and to determine how varying degrees of liver quality affect experimental outcomes. Over one
hundred human livers were categorized according to initial viability, as assessed by ATP content, K+ retention, protein synthesis, and LDH leakage. Each liver was placed in a low-, a medium-, or a high-quality group. The results
showed that 76% of transplant-grade tissue (procured for transplantation) fell into the high-viability classification while
the majority of research-grade tissue (not procured for transplantation) fell into the lowest viability classification. It
was also found that only tissue slices prepared from highly viable human liver could be cold-preserved and cryopreserved.
Dichlorobenzene metabolism was also greater in slices from highly viable human livers as compared to less viable livers. This
study showed that human liver tissue acquired for medical research substantially varies in its viability and that these differences
will affect the experimental data obtained.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
10.
Glycolipid transfer protein from bovine brain 总被引:2,自引:0,他引:2
Glycolipid transfer protein from bovine brain has been purified partially by ammonium sulfate precipitation, CM-52 ion-exchange, and Sephadex G-75 column chromatography. Both pyrene-labeled and tritium-labeled glucocerebrosides have been used to study the kinetics of protein-mediated transfer between donor and acceptor vesicles. Protein accelerates glucocerebroside transfer but does not accelerate phospholipid transfer. In colyophilized small sonicated vesicles (10% glucocerebroside, 90% 1-palmitoyl-2-oleoyl-phosphatidylcholine) about two-thirds of the glycolipid is transferred in 2 h and the remaining one-third does not transfer (up to 5 h). For donor and acceptor vesicles made of dipalmitoylphosphatidylcholine or 1-palmitoyl-2-oleoyl-phosphatidylcholine, glucocerebroside (10% in donors) is transferred rapidly only when both the donor and acceptor matrix phospholipids are in the liquid-crystalline state. If either donor or acceptor vesicles are in the gel state, transfer protein mediated transfer is much reduced. The amount of transfer protein bound specifically to glucocerebroside-containing vesicles is nearly equal above and below the matrix phospholipid phase transition temperature. Bound protein transfers glucocerebroside upon addition of acceptor vesicles. 相似文献
11.
Role of glycerol 3-phosphate and glycerophosphate acyltransferase in the nutritional control of hepatic triacylglycerol synthesis 总被引:7,自引:7,他引:0
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
1. Glycerol 3-phosphate content of isolated hepatocytes from starved rats and of glycogen-depleted hepatocytes from fed rats was low and severely limited triacylglycerol synthesis. 2. Raising the glycerol 3-phosphate content by addition of precursors to the cells resulted in a hyperbolic-like relationship between triacylglycerol synthesis and cellular glycerol 3-phosphate content. Statistical analysis of the curves showed no significant differences between the nutritional states either at saturating or at subsaturating glycerol 3-phosphate content. 3. Vmax. of glycerophosphate acyltransferase measured in homogenized hepatocytes was decreased by 30–40% in starvation. There was no change in apparent Km for glycerol 3-phosphate. Since at saturating glycerol 3-phosphate content esterification rates in hepatocytes of both nutritional states were identical, the enzyme is not limiting esterification under this condition. 4. At subsaturating glycerol 3-phosphate content the flux through glycerophosphate acyltransferase necessarily limits esterification. Therefore one would expect a decrease in esterification in starvation under this condition. This was the case when triacylglycerol synthesis was plotted against intracellular glycerol 3-phosphate concentration, calculated from the cellular glycerol 3-phosphate content and the intracellular water space, which was smaller in hepatocytes from starved rats. 5. The data obtained in hepatocytes were extrapolated to the intact liver by using the number of parenchymal cells per g of liver as determined from marker-enzyme analysis and the liver weight per 100g body weight. The extrapolation suggested that glycerol 3-phosphate is limiting esterification in vivo for contents below 0.3–0.4 and 0.5–0.65μmol/g for livers from fed and starved animals respectively. Also for a given fatty acid load and a glycerol 3-phosphate content below 0.3μmol/g the liver may esterify less in the starved state. However, at the glycerol 3-phosphate contents measured in freeze-clamped livers (0.30 and 0.44μmol/g for the fed and starved state respectively), livers in both nutritional states seemed capable of esterifying similar amounts of fatty acids. 相似文献
12.
A cytofluorometric study was made of total glycogen in rat liver cells in the norm and upon the chronic intoxication with CCl4. The liver cells were obtained from rats by means of intravital needle aspiration biopsy at the beginning of the experiment, after 3, and 6 months, and 1 month after partial hepatectomy of control and cirrhotic livers. Glycogen contents in liver cells were attributed to dry weight measured interferometrically. Upon the long-term chronic intoxication of rats with the hepatotropic poison the glycogen content increased by 1.4-2.5 times, and in some cells of cirrhotic livers even by 5-5.5 times compared to the normal level. 1 month after the resection both glycogen content and rat liver cell morphology were seen almost close to the normal. The data are discussed in terms of results earlier reported elsewhere on the increase of glycogen content in liver cells of patients with chronic hepatitis. 相似文献
13.
Glucocerebrosidase deficiency and lysosomal storage of glucocerebroside induced in cultured macrophages 总被引:2,自引:0,他引:2
Pijush K. Das Gary J. Murray Andrew E. Gal John A. Barranger 《Experimental cell research》1987,168(2):463-474
A cell culture model stimulating the genetic deficiency of glucocerebrosidase has been developed, utilizing macrophages and conduritol B epoxide (CBE), the specific irreversible inhibitor of the enzyme. Rat peritoneal macrophage glucocerebrosidase was completely inhibited when cells were treated with 10 microM CBE for 16 h or 100 microM CBE for 2 h. The t1/2 of inactivation was 30 min at 10 microM concentration. When cells were washed free of CBE, the enzyme activity reappeared linearly with time, reaching 50% of control activity 48 h after removal of the inhibitor. CBE-treated macrophages have normal phagocytic activity toward [3H]glycine-coupled latex beads and a normal number of mannose receptors. CBE was found to have no effect on other lysosomal enzymes. When [14C]glucocerebroside, encapsulated in multilamellar liposomes with alpha-D-mannopyranoside covalently coupled to the surface, was fed to glucocerebrosidase-depleted macrophages, the radiolabelled glycolipid accumulated and was undegraded. Subcellular fractionation on a Percoll density gradient demonstrated that the stored glucocerebroside in the CBE-treated macrophages was localized in lysosomes. 相似文献
14.
A computer-centered spectrofluorimeter was used to examine the physicochemical properties of hepatic microsomes and microsomal lipids obtained from isolated rat livers perfused with medium containing palmitate or oleate. The fatty acid composition and degree of unsaturation of the liver microsomal lipids reflected that the fatty acid present in the perfusate. The absorption corrected fluorescence, relative fluorescence efficiency, polarization, and fluorescence anisotropy of several fluorescent probe molecules were measured to determine if their different microenvironments may be altered by the type of fatty acid infused. The probe molecules β-parinaric acid and 1.6-diphenyl-1,3,5-hexatriene had higher values for each of these parameters when incorporated into microsomes obtained from livers perfused with a medium containing palmitate than with oleate. The same parameters measured for cholesta-5,7,9(11)-trien-3β-ol and N-phenyl-1-naphthylamine were not altered. These differences appeared to be primarily due to alterations in microviscosity of the probe microenvironments since the rotational correlation time of 1,6-diphenyl-1,3,5-hexatriene was 25% lower in the microsomes from livers perfused with oleate as compared to livers perfused with palmitate. Thermal discontinuities in Arrhenius plots were noted in the intact microsomes but not in the isolated microsomal lipids with the fluorescence probe molecule β-parinaric acid. Break points occurred at 10°C and 26°C for microsomes from livers perfused with palmitate and at 12°C and 17°C for microsomes from livers perfused with oleate containing medium. These results suggest that the physicochemical properties of liver microsomes were determined in part by the fatty acid in the perfusate. 相似文献
15.
《生物化学与生物物理学报:疾病的分子基础》1993,1225(1):71-77
Spectral changes in human hepatic tumours and possible systemic effects of tumour on host liver were assessed by 31P amnd 1H in vitro NMR spectroscopy. The 1H and 31P spectra from liver tumour biopsies showed significant elevation in phosphoethanolamine, phosphocholine, taurine, citrate, alanine, lactate and glycine, and significant reduction in GPE (glycerophosphoethanolamine), GPC (glycerophosphocholine), creatine and threonine compared to histologically normal tissue. 31P-NMR spectra obtained from histologically normal tissue within tumour-bearing livers showed significant elevation in phosphoethanolamine and phosphocholine compared to data from liver biopsies from nontumour-bearing patients (pancreatitis). These results suggest that alterations in membrane metabolism in host liver can be detected by 31P-NMR. 相似文献
16.
17.
Shawn Doonan Diona H. Koerner Wolfgang Schmutzler Charles A. Vernon 《The Biochemical journal》1974,144(3):533-541
The threonine dehydratase extracted from sheep liver is in an essentially inactive form, referred to here as the precursor, but can be activated by incubation at high temperature in alkaline solution. A method for purification of the activated enzyme to a state approaching homogeneity has been devised. The activated enzyme catalyses the deamination of serine but rapidly loses activity during the process. The enzyme inactivated by incubation with serine can be reactivated under the same conditions as those described for the precursor, the kinetic parameters being the same in both cases. Individual sheep livers differ widely in their content of threonine dehydratase, and the possible role of dietary factors in this variability has been examined. The average amount of the enzyme in the livers of sheep fed on high-plant-protein diets did not differ significantly from that in livers obtained from slaughterhouses, but was higher than that in livers from animals fed only on grass or normal concentrates. Large increases in enzyme concentration were, however, obtained when sheep were injected intraperitoneally with a protein hydrolysate. The enzyme from the livers of these sheep could be purified by the same technique and to the same specific activity as the enzyme from the livers of control sheep. 相似文献
18.
A dialysis procedure for hypotonic hemolysis has been developed in which erythrocytes can be loaded with water-soluble enzymes, detergent-solubilized enzymes (glucocerebrosidase) and detergent-dispersed glycolipid (glucocerebroside). The procedure allows approx. 40–50% of the added enzyme or glcyolipid to be encapsulated. The final intracellular concentration of enzyme or glycolipid is about equal to the extracellular concentration. The loaded cells can be ingested by macrophage in vitro and the glucocerebroside partially degraded by lysosomal glucocerebrosidase. The use of this procedure for the investogation of Gaucher's disease is discussed. 相似文献
19.
Bote G. Bruinsma Wilson Wu Sinan Ozer Adam Farmer James F. Markmann Heidi Yeh Korkut Uygun 《PloS one》2015,10(3)
Background
Liver transplantation plays a pivotal role in the treatment of patients with end-stage liver disease. Despite excellent outcomes, the field is strained by a severe shortage of viable liver grafts. To meet high demands, attempts are made to increase the use of suboptimal livers by both pretransplant recovery and assessment of donor livers. Here we aim to assess hepatic injury in the measurement of routine markers in the post-ischemic flush effluent of discarded human liver with a wide warm ischemic range.Methods
Six human livers discarded for transplantation with variable warm and cold ischemia times were flushed at the end of preservation. The liver grafts were flushed with NaCl or Lactated Ringer’s, 2 L through the portal vein and 1 L through the hepatic artery. The vena caval effluent was sampled and analyzed for biochemical markers of injury; lactate dehydrogenase (LDH), alanine transaminase (ALT), and alkaline phosphatase (ALP). Liver tissue biopsies were analyzed for ATP content and histologically (H&E) examined.Results
The duration of warm ischemia in the six livers correlated significantly to the concentration of LDH, ALT, and ALP in the effluent from the portal vein flush. No correlation was found with cold ischemia time. Tissue ATP content at the end of preservation correlated very strongly with the concentration of ALP in the arterial effluent (P<0.0007, R2 = 0.96).Conclusion
Biochemical injury markers released during the cold preservation period were reflective of the duration of warm ischemic injury sustained prior to release of the markers, as well as the hepatic energy status. As such, assessment of the flush effluent at the end of cold preservation may be a useful tool in evaluating suboptimal livers prior to transplantation, particularly in situations with undeterminable ischemic durations. 相似文献20.
Phenotypic differences in expression of cytochrome P-450g but not its mRNA in outbred male Sprague-Dawley rats 总被引:1,自引:0,他引:1
P McClellan-Green D J Waxman M Caveness J A Goldstein 《Archives of biochemistry and biophysics》1987,253(1):13-25
Cytochrome P-450g was isolated from livers of adult male Sprague-Dawley (CD) rats. Antibody to P-450g cross-reacted with several proteins in Western blots of liver microsomes from male CD rats. An immunospecific antibody was prepared by adsorption over immunoaffinity columns of Sepharose-bound solubilized rat liver microsomes from female CD and male Fischer 344 rats containing little or no P-450g. The immunopurified antibody recognized a single protein on Western blots of liver microsomes from male CD rats with an electrophoretic mobility identical to that of P-450g. Using this antibody, P-450g was shown to be male specific in the CD rat and expressed at maturity. Adult male CD rats were shown to fall into two distinct populations, those expressing high levels of P-450g (+g) and those expressing low levels of P-450g (-g). The P-450g content of the two populations differed 10- to 20-fold. P-450g was low or absent in liver microsomes of both sexes of adult Fischer rats. Purified P-450g catalyzed the hydroxylation of testosterone and androstenedione principally at the 6 beta-position and progesterone at the 16 alpha- and 6 beta-positions in reconstituted systems. However, the hydroxylation of these steroids by liver microsomes from the (+g) phenotype did not differ from that of the (-g) phenotype. Translatable mRNA for P-450g could be detected in livers of adult male CD rats but not female rats. However, the level of P-450g mRNA in livers of adult male CD rats with the (+g) phenotype did not differ from that of (-g) phenotype. These data suggest that phenotypic differences in the expression of P-450g do not depend on differences in mRNA content. This study provides a clear example of a P-450 isozyme which is markedly variable in an outbred strain of rat and absent in an inbred strain. Such a marked variability in an enzyme involved in metabolism of endogenous and exogenous substrates could account for some of the strain differences in susceptibility to toxic chemicals. 相似文献