Biomedical subjects

D S Goodman

Publications and source records attributed to D S Goodman.

At least 55 records · Page 3Linked to original sources

PubMed1987

The role of arachidonic acid metabolites in cardiovascular homeostasis. Biochemical, histological and clinical cardiovascular effects of non-steroidal anti-inflammatory drugs and their interactions with cardiovascular drugs.

Derivatives of arachidonic acid may be involved in atherosclerosis and its clinical complications. There is much interest in pharmacologically manipulating the arachidonic acid cascade as a means of preventing cardiovascular disease. The development of atherosclerosis has been intensively studied and the consequences of cardiovascular or cerebrovascular vessel occlusion are too familiar. Many factors are probably involved, but the role of plasma lipoproteins and the interactions between various constituents of blood and blood vessel walls have received particular attention. The risk of cardiovascular disease associated with high plasma concentrations of the low density lipoproteins and the possible protective effects of high density lipoproteins have been well documented. Much is now known about lipoprotein biochemistry, and the importance of controlling the quantity and quality of dietary lipids has been demonstrated in epidemiological studies. In studies of patients with transient ischaemic attacks, aspirin reduced the risk of stroke and death in males, although these benefits were not as convincingly demonstrated in women. The majority of patients were given aspirin 1300 mg daily, but the optimum dosage was not properly evaluated. Administering aspirin in combination with another antiplatelet drug did not appear to offer any therapeutic advantage in these patients. Aspirin showed a positive, but non-significant trend towards reduced numbers of cardiac events, non-fatal infarcts and total mortality in patients who had experienced at least one myocardial infarction. In contrast, statistically significant beneficial effects were recorded when patients with unstable angina were administered aspirin. The risks of myocardial infarction or coronary death were reduced by 51% in 2 large studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

PubMed1987

Subcellular localization of retinoids, retinoid-binding proteins, and acyl-CoA:retinol acyltransferase in rat liver.

Studies were conducted to define the subcellular localization of endogenous retinoids (vitamin A), retinoid-binding proteins, and acyl-CoA:retinol acyltransferase (ARAT) in liver and to determine whether their distributions were affected by hepatic vitamin A content. Quantitative subcellular fractionation techniques were used. Rats were fed purified diets either containing or lacking vitamin A to obtain animals with total retinoid stores ranging from 0.5 to 172 micrograms of retinol equivalent per gram of liver. Liver homogenates were fractionated by differential centrifugation to yield nuclear (N), mitochondrial-lysosomal (ML), microsomal (P), and high-speed supernatant (S) fractions. N, ML, and P were washed two more times by resuspension and centrifugation to remove constituents bound nonspecifically. S was further resolved into "floating lipid" and underlying "cytosol" by prolonged ultracentrifugation. The distributions of marker constituents were not affected by vitamin A status. Most of the retinyl ester in the liver was recovered in the S fraction where it was entirely (greater than 95%) associated with floating lipid. About half of the total free retinol was also recovered in the S fraction, but it was mostly (2/3) associated with cytosol per se. A substantial portion (30%) of the free retinol was recovered in the 3 X -washed microsomal (P) fraction. Sufficient binding capacity for retinol was present in both P (as retinol-binding protein) and S (as cellular retinol-binding protein) to quantitatively account for the amounts of free retinol present in the two fractions. ARAT activity in the liver was distributed among the subcellular fractions in a manner identical with an endoplasmic reticulum marker enzyme (NADPH-cytochrome C reductase).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyltransferases↗

PubMed1986

Immunologic and enzymatic comparisons between human and bovine lipoprotein lipase.

Studies were conducted to compare human and bovine lipoprotein lipase (LPL) preparations with regard to immunological cross-reactivity and substrate specificity. LPL was partially purified from human milk. An antiserum against the human LPL preparation was produced in a goat. This antiserum inhibited LPL enzymatic activity in human milk and in human post-heparin plasma. Neither bovine milk nor bovine post-heparin plasma LPL enzymatic activity was inhibited by this antiserum. These findings suggest that there are significant structural differences between the human and bovine enzymes in domains that are involved in enzymatic activity. Human and bovine post-heparin plasma and partially purified preparations of LPL from human and bovine milk were compared with regard to substrate specificity, by comparing their lipolytic activities against triglyceride, cholesteryl esters, and retinyl esters. Only the partially purified bovine milk LPL preparation possessed retinyl palmitate hydrolase activity. The results suggest that this latter activity may be the result of a previously unrecognized contaminant in the commonly used LPL preparations from bovine milk.

Animals↗

PubMed1986

Effects of mevinolin and mevalonate on cell growth in several transformed cell lines.

Studies were conducted to explore the effects of mevinolin, a competitive inhibitor of HMG CoA reductase, on the growth and morphology of normal and transformed murine fibroblasts. Mevinolin is known to block DNA synthesis and cell growth in a number of kinds of non-transformed cells. Eight cell lines were studied, including two normal fibroblast cell lines (C3H 10T 1/2 and NIH 3T3) and derivatives of these cell lines transformed by chemical carcinogens, X-irradiation or the H-ras oncogene. All of the eight cell lines displayed appreciable growth inhibition by 5 microM mevinolin and marked inhibition by 30 microM mevinolin. Mevinolin also induced a marked rounding in the morphology of all of the cell lines. These effects of mevinolin on cell growth and morphology were blocked or reversed by the addition of mevalonic acid. Thus, both normal and transformed cells require mevalonate, or an as yet unidentified metabolite of mevalonate for their growth, even though some transformed cells have become relatively autonomous of other growth factors. Whereas mevinolin acted primarily as a cytostatic agent for most of the cell lines studied, with the transformed cell line MCA/10T 1/2, which ordinarily grows to a very high cell density, prolonged exposure to mevinolin caused marked cytotoxicity. Thus mevinolin might be useful as an anti-tumor agent for specific tumors.

Animals↗

PubMed1986

Retinol-binding protein and transthyretin mRNA levels in visceral yolk sac and liver during fetal development in the rat.

Studies were conducted to explore the synthesis of retinol-binding protein and transthyretin by embryonic and extraembryonic tissues during fetal development in the rat. The levels of retinol-binding protein mRNA and transthyretin mRNA were measured in fetal liver and in extraembryonic tissues by RNA gel blot analysis and hybridization with specific cDNA probes. Retinol-binding protein mRNA and transthyretin mRNA were both detected in the liver of fetuses at 14 days of gestation. The relative levels of these two transcripts increased during later fetal development; by the 20th day of gestation retinol-binding protein mRNA levels were comparable to those of the adult liver, while the levels of transthyretin mRNA were only 46% of those of the adult liver. Examination of the extraembryonic membranes for retinol-binding protein mRNA and transthyretin mRNA showed that these two transcripts were present specifically and only in the visceral yolk sac. The relative levels of retinol-binding protein mRNA and transthyretin mRNA in visceral yolk sac were constant from 14 to 20 days of gestation, averaging 58% and 51%, respectively, of the adult liver levels of these two transcripts. Both retinol-binding protein mRNA and transthyretin mRNA in the visceral yolk sac were found to be specifically localized in the endodermal layer. Finally, both immunoprecipitable retinol-binding protein and transthyretin were found to be synthesized and secreted by explant cultures of visceral yolk sac tissue. These data show that the visceral yolk sac is a major source of both retinol-binding protein and transthyretin in the developing fetus. Since the visceral yolk sac is a site of true placentation and nutrient transfer in the rodent, this raises the possibility that visceral yolk sac-derived retinol-binding protein and transthyretin may play important roles in the transport and delivery of retinol from the maternal blood to the developing fetus.

Animals↗

PubMed1986

Serum retinol and retinol-binding protein levels do not predict subsequent lung cancer.

Retinol and retinol-binding protein levels were measured in sera previously obtained, and stored in the frozen state, at multiphasic health checkups from 151 persons subsequently found to have lung cancer (cases) and 302 persons who remained free of cancer (controls). Two controls were matched to each case for sex, skin color, age, date of multiphasic health checkup, and aspects of the smoking habit. Mean levels in cases and controls were, respectively, retinol: 82.17 and 82.37 micrograms/dl (p = 0.93), and retinol-binding protein: 6.04 and 6.00 mg/dl (p = 0.81). Mean differences between cases and controls were, retinol: 0.195 micrograms/dl with 95% confidence limits, -3.91 and 4.30 micrograms/dl; retinol-binding protein: -0.033 mg/dl with 95% confidence limits, -0.31 and 0.24 mg/dl. No significant trend in relative risk of lung cancer was observed when the retinol or retinol-binding protein distribution was divided into quintiles. No significant associations were observed in subgroups based on age, sex, histologic type of cancer, cigarette consumption, or interval between blood drawing and cancer diagnosis. In this large study, retinol and retinol-binding protein levels were not useful in predicting the subsequent development of lung cancer.

Adult↗

PubMed1986

Localization of immunoreactive transthyretin (prealbumin) and of transthyretin mRNA in fetal and adult rat brain.

We used a combination of immunohistochemical and molecular-biological techniques to investigate the localization of transthyretin (TTR) in the brains of adult and fetal rats. The immunohistochemical studies employed antibodies purified by immunosorbent affinity chromatography, permitting the specific staining and localization of TTR using the unlabeled peroxidase-antiperoxidase method. TTR mRNA levels were measured by Northern-blot analysis of poly (A+) RNA, followed by hybridization to 32P-labeled TTR cDNA; TTR mRNA was localized in brain tissue sections by in situ hybridization. Immunoreactive TTR was found to be specifically localized in the choroid plexus epithelial cells of adult rat brain. High levels of TTR mRNA were found in poly (A+) RNA samples obtained from the choroid plexus. In addition, the specific localization of TTR mRNA in the epithelial cells of the choroid plexus was demonstrated by in situ hybridization. Neither immunoreactive TTR nor TTR mRNA were found in other regions of adult rat brains. The levels of TTR mRNA in the choroid plexus were at least 30 times higher than those observed in the adult liver. Immunoreactive TTR was observed in the brains of fetal rats on as early as the 11th day of gestation. This immunoreactive TTR was localized in the tela choroidea, the developmental forerunner of the choroid plexus. Immunoreactive TTR was also observed in the fetal choroid plexus as it began to form (14th day of gestation) as well as in the more completely developed choroid plexus (18th day of gestation).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1986

Genetic expression of a transthyretin mutation in typical and late-onset Portuguese families with familial amyloidotic polyneuropathy.

Two studies were conducted to explore questions concerning the expression of a mutant transthyretin (TTR) gene, found in Portuguese patients with familial amyloidotic polyneuropathy (FAP). In a kindred with typical onset of the disease, complete agreement between genotype and phenotype was seen for all carriers of the variant TTR with a methionine-for-valine substitution at position 30 (TTR[Met30]). In another study involving a FAP kindred with a late onset of clinical disease, TTR(Met30) was found in plasma in asymptomatic persons with ages above the usual age of onset of the disease. No evidence was obtained for the existence of a different mutation in TTR or for repression of the expression of the mutant TTR gene in this kindred. The factors responsible for the delay in the development of clinical manifestations in late-onset patients are not known and warrant further study.

Adolescent↗

PubMed1986

Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award.

Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.

Animals↗

PubMed1986

Presence of a plasma transthyretin (prealbumin) variant in familial amyloidotic polyneuropathy in a kindred of Greek origin.

Human plasma transthyretin (TTR, a protein formerly called prealbumin) is known to be associated with familial amyloidotic polyneuropathy (FAP) of autosomal inheritance. A variant TTR with a methionine-for-valine substitution at position 30 has been described as the major protein component of amyloid in Portuguese and Japanese patients with FAP and in patients of Swedish ancestry with FAP. In these patients, TTR(Met30) also circulates in relatively low concentration in the plasma. TTR variants having substitutions in other positions have also been reported in a patient of Jewish origin with FAP. We now report studies on TTR from an FAP kindred of Greek ancestry. By peptide mapping analysis, plasma TTR from the propositus was compared with TTR from a Portuguese patient with FAP. TTR(Met30) was found to circulate in the blood plasma of the Greek propositus. By use of a recently developed immunoblotting technique, this variant TTR was also detected in some of the relatives of the propositus. Future studies of this mutant gene among ethnically different FAP populations might contribute to an understanding of selection and persistence of the mutation.

Amino Acid Sequence↗

PubMed1986

Effects of dietary retinoic acid on cellular retinol- and retinoic acid-binding protein levels in various rat tissues.

A study was conducted to explore the effects of retinoic acid, fed to retinol-deficient rats, on the tissue distribution and levels of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP). Sensitive and specific radioimmunoassays were employed to measure the levels of both CRBP and CRABP. Two groups of six male rats each were fed a purified retinoid-deficient diet supplemented with either: i) retinyl acetate (control group); or ii) retinoic acid (30 mg/kg diet) (retinol deficient-retinoic acid group). The retinoic acid supplementation was begun after 38 days on the retinoid-deficient diet alone, and was continued for 52-54 days. Analysis of the data indicated that only the CRBP level of the proximal epididymis in the retinol-deficient/retinoic acid group differed significantly from (was lower than) the corresponding control level, at the 1% confidence level. CRABP tissue levels did not differ significantly between the two groups. Thus, a moderately large intake of retinoic acid, as the only source of retinoids, had very little effect on the tissue distribution or levels of either its own cellular binding protein (CRABP) or of CRBP. This study provides further information showing that the tissue levels of the cellular retinoid-binding proteins are highly regulated and maintained in rats, even in the presence of marked changes in retinoid nutritional status.

Animals↗

PubMed1986

Lack of relationship in humans of the parameters of body cholesterol metabolism with plasma levels of subfractions of HDL or LDL, or with apoE isoform phenotype.

The factors involved in regulating parameters of whole body cholesterol metabolism in humans have been explored in a series of investigations. Several physiological variables have been identified (weight, excess weight, plasma cholesterol, and age) that can predict 53-76% of the variation in production rate (PR) and in the sizes of the rapidly exchanging pool of body cholesterol (M1) and of the minimum estimates of the slowly exchanging pool of body cholesterol (M3min) and of total body cholesterol (Mtotmin). Surprisingly, measurements of the plasma levels of HDL cholesterol and of the major HDL apolipoproteins (apoA-I, A-II, and E) did not provide additional information useful in predicting parameters of whole body cholesterol metabolism. A study was therefore conducted to investigate possible relationships of the plasma levels of subfractions of lipoproteins, determined by analytic ultracentrifugation, and of apoprotein E phenotype, with the parameters of whole body cholesterol metabolism. Ultracentrifugal analysis of plasma lipoprotein subfractions was performed at the Donner Laboratory in 49 subjects; all of these subjects were currently undergoing whole body cholesterol turnover studies or had previously had such studies and were in a similar metabolic state as judged by plasma lipid and lipoprotein values. Apoprotein E phenotyping was carried out in 71 subjects. Differences in model parameters were sought among subjects with various apoprotein E phenotypes. Ultracentrifugal LDL subfractions Sof 0-2 (the region of LPa), Sof 0-7 (smaller LDL), Sof 7-12 (larger LDL), Sof 12-20 (IDL), and ultracentrifugal HDL subfractions Fo1.20 0-1.5 (smaller HDL3), Fo1.20 2-9 (larger HDL3 plus HDL2), and Fo1.20 5-9 (larger HDL2 or HDL2b) were examined for correlations with each other and with parameters of whole body cholesterol metabolism.

Adolescent↗

PubMed1986

Retinol-binding protein messenger RNA levels in the liver and in extrahepatic tissues of the rat.

A retinol-binding protein (RBP) cDNA clone was used to examine the effect of retinol status on the level of RBP mRNA in the liver, and to explore whether extrahepatic tissues contain RBP mRNA. In the first series of experiments, poly(A+) RNA was isolated from the livers of normal, retinol-depleted, and retinol-repleted rats and the levels of RBP mRNA in these samples were determined by both Northern blot and RNA Dot blot analyses. The levels of RBP mRNA in liver were similar in all three groups of rats. These findings confirm and extend previous studies which showed that retinol did not alter the in vivo rate of RBP synthesis or the translatable levels of RBP mRNA. In a second series of experiments, the RBP cDNA clone was used to survey poly (A+) RNA isolated from 12 different rat tissues for RBP mRNA by Northern blot analysis. We found that, along with the liver, many extrahepatic tissues contained RBP mRNA. Kidney contained RBP mRNA at a level of 5-10% of that of the liver, and the lungs, spleen, brain, stomach, heart, and skeletal muscle contained 1-3% of that of the liver. Translation of kidney poly (A+) RNA in rabbit reticulocyte lysates and immunoprecipitation of the translation products with anti-RBP antiserum resulted in a protein band of the same size as liver preRBP. These data suggest that RBP is synthesized in many extrahepatic tissues. It is possible that this extra-hepatically synthesized RBP may function in the recycling of retinol from these tissues back to the liver or to other target organs.

Animals↗

PubMed1985

Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells.

The main retinoids and some binding proteins and enzymes involved in retinol metabolism have been quantified in different types of rat liver cells. Hepatic perisinusoidal stellate cells contained 28-34 nmol of retinoids/10(6) cells, and parenchymal liver cells contained 0.5-0.8 nmol of retinoids/10(6) cells, suggesting that as much as 80% of more of total liver retinoids might be stored in stellate cells with the rest stored in parenchymal cells. Isolated endothelial cells and Kupffer cells contained very low levels of retinoids. More than 98% of the retinoids recovered in stellate cells were retinyl esters. Isolated parenchymal and stellate cell preparations both contained considerable retinyl palmitate hydrolase and acyl-CoA:retinol acyltransferase activities. Parenchymal cells accounted for about 75-80% of the total hepatic content of these two enzyme activities, with the rest located in stellate cells. On a cell protein basis, the concentrations of both of these activities were much greater in stellate cells than in parenchymal cells. In contrast, cholesteryl oleate and triolein hydrolase activities were fairly evenly distributed in all types of liver cells. Large amounts of cellular retinol binding proteins were also found in parenchymal and stellate cells. Although parenchymal cells accounted for more than 90% of hepatic cellular retinol binding protein, the concentration of the protein in stellate cells (per unit protein) was 22 X greater than that in parenchymal cells. Stellate cells were also enriched in cellular retinoic acid binding protein. Thus, both parenchymal and stellate cells contain substantial amounts of retinoids and of the enzymes and intracellular binding proteins involved in retinol metabolism. Stellate cells are particularly enriched in these several components.

Acyltransferases↗

PubMed1985

Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat.

Studies were conducted to ascertain if transthyretin mRNA was present in extrahepatic tissues of the rat. A trnasthyretin cDNA clone was isolated from a lambda gt11 human liver cDNA library by antibody screening and its identity was confirmed by nucleotide sequence analysis. This transthyretin cDNA clone was used to survey poly(A+) RNA isolated from 12 different rat tissues for transthyretin mRNA by Northern blot analysis. The liver contained the highest level of transthyretin mRNA and this level was not altered by the vitamin A status of the rat. A significant amount of transthyretin mRNA was found in the brain (30% of the level of the liver) which was localized in specific regions of the brain. In addition, detectable levels of transthyretin mRNA (1% to 2% of that of the liver) were observed in the stomach, heart, skeletal muscle, and spleen. Translation of brain poly(A+) RNA in rabbit reticulocyte lysates and immunoprecipitation of the translation products with anti-transthyretin antiserum resulted in a protein band of the same size as liver pre-transthyretin. Liver pre-transthyretin was processed by the cotranslational addition of dog pancreas microsomal membranes to a protein that migrated coincidentally with monomeric serum transthyretin. These data suggest that transthyretin in the brain and the cerebrospinal fluid results from de novo synthesis and that transthyretin may play a significant physiological function, as yet unknown, within the nervous system.

Animals↗

PubMed1985

Influence of retinoid nutritional status on cellular retinol- and cellular retinoic acid-binding protein concentrations in various rat tissues.

Studies were conducted to explore the effects of differences in retinoid nutritional status and of sex on the tissue distribution and levels of cellular retinol-binding protein (CRBP) and of cellular retinoic acid-binding protein (CRABP) in the rat. Sensitive and specific radioimmunoassays were developed and employed to measure the levels of both CRBP and CRABP. Four groups of six male rats each were fed experimental diets that differed greatly in the amount and kind of retinoids provided, but were otherwise identical. These groups were comprised of rats that were normal controls, retinoid-deficient, retinoic acid-fed, and excess retinol-fed. A fifth group of six female rats was fed the control diet. Immunogens identical with rat testis CRBP and CRABP, as assessed by radioimmunoassay displacement curves, were found in every rat tissue examined (21 tissues in males, 18 in females). The highest levels of CRBP were found in the proximal portion of the epididymis, the liver, and kidney. The highest levels of CRABP were found in the seminal vesicles, vas deferens, and skin. A significant (p less than 0.01) inverse relationship was found between CRBP and CRABP levels in the different tissues of the male reproductive tract. In both males and females, CRBP levels were highest in the gonads and proximal portion of the reproductive tract and decreased distally, whereas the opposite was true for CRABP. Retinoid-deficient rats showed reduced tissue levels of CRBP; thus, tissue CRBP levels are influenced by diet and retinoid availability. No differences in tissue CRBP levels were found in the rats fed the control, the retinoic acid, or the excess retinol diets. Female control rats had higher CRBP levels than male controls in 4 of 15 tissues compared (liver, lung, thymus, and fat). In contrast, tissue CRABP levels showed no diet- or sex-dependent differences. Only in one tissue, the skin, were differences observed (lower CRABP in retinoid-deficient and in female rats). Thus, CRABP metabolism and levels appear to be minimally influenced by the amount or kind of retinoid ligand available or by sex.

Animals↗

PubMed1985

Structure-function relationships of retinoids in their effects on retinol-binding protein metabolism in cultured H4II EC3 liver cells.

Studies were conducted to explore the structural features of retinoids that may be required to stimulate the secretion or production of retinol-binding protein (RBP) by H4II EC3 rat hepatoma cells in culture. Sixteen retinoids, that differed from all-trans-retinol in the cyclohexene ring, the polyene side chain, and/or the functional end group, were each incubated with H4II EC3 cells, and RBP secretion and accumulation were determined by radioimmunoassay. A number of retinoids, in addition to retinol, effectively stimulated RBP secretion. The results suggest that an intact cyclohexene ring may be necessary for the stimulation of RBP secretion. In contrast the system did not exhibit much specificity with regard to either the structure of the side chain or the nature of the end group. No relationship was found between the ability of a retinoid to stimulate RBP secretion and production and its biological activity. The biologically active retinoid, 13-cis-retinoic acid, was inactive in the present system, whereas the biologically inactive perhydromonoeneretinol was moderately effective in stimulating both RBP secretion and accumulation. In contrast, there appeared to be some relationship between the ability of different retinoids to stimulate RBP secretion and their ability to bind to RBP. In general, retinoids that had previously been shown to bind to RBP produced a greater stimulation of RBP secretion than those that did not bind to RBP. The secretion of RBP obtained with a given retinoid was not well correlated with the net accumulation of RBP. For example, retinoyl amide did not stimulate RBP secretion but was moderately effective in stimulating RBP accumulation. Thus, the secretion of RBP does not appear to be necessary for the stimulation of the net accumulation of RBP.

Animals↗

PubMed1985

Plasma and cellular retinoid-binding proteins and transthyretin (prealbumin) are all localized in the islets of Langerhans in the rat.

The immunohistochemical localization of plasma retinol-binding protein (RBP), cellular retinol-binding protein (CRBP), and transthyretin (TTR) was studied in rat pancreas. The studies employed antibodies purified by immunosorbent affinity chromatography, permitting the specific staining and localization of each antigen by the unlabeled peroxidase-antiperoxidase method. Specific immunostaining for each of these three proteins was found localized to the islets of Langerhans. Both RBP and CRBP were localized in cells that were peripherally distributed within the islets, with an anatomic distribution that resembled that of the glucagon-containing A cells. Immunoreactive TTR was localized in cells that were more centrally distributed in the islets, with an anatomic distribution that resembled that of the insulin-containing B cells. These findings were confirmed by radioimmunoassay of a homogenate of isolated rat islets. By using sensitive and specific radioimmunoassays for each antigen, unusually high levels of CRBP, RBP, TTR, and cellular retinoic acid-binding protein (CRABP) were found in rat islets. The physiological significance of the localization of RBP, CRBP, CRABP, and TTR in the islets is not known. The findings suggest that retinoids and their binding proteins may play important metabolic roles within islet cells, and hence that they may be involved in some way in the biological, endocrine, function of the islets.

Animals↗