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Biomedical subjects

R Gander

Publications and source records attributed to R Gander.

13 recordsLinked to original sources
PubMed2003

Molecular characterization of rabbit scavenger receptor class B types I and II: portal to central vein gradient of expression in the liver.

To further elucidate the role of scavenger receptor class B type I (SR-BI) in reverse cholesterol transport and in atherogenesis, we performed studies in the rabbit, an animal model displaying a lipoprotein profile similar to that of human, expressing cholesteryl ester transfer protein in plasma and having been demonstrated to be susceptible to atherosclerosis. In this report, we describe for the first time the isolation and characterization of rabbit cDNA fragments encoding SR-BI and scavenger receptor class B type II (SR-BII). Development of an isoform-specific Taqman Real Time PCR system and generation of isoform-specific polyclonal antibodies allowed us to measure SR-BI and SR-BII expression in various rabbit organs on mRNA and protein levels, respectively. We found the highest expression of SR-BI in adrenal gland, liver, and proximal intestine; lesser expression was found in appendix and spleen. Immunohistochemical staining of frozen sections showed SR-BI expression in the cortex but not in the medulla of adrenal gland. An increasing portal to central vein gradient of expression was found within the hepatic lobule. As shown in this report, identification and characterization of SR-BI expression in the rabbit affords a powerful tool to elucidate the role of SR-BI in cholesterol homeostasis and atherogenesis in human.

Adrenal Cortex↗
PubMed2003

TGF-beta cytokines increase senescence-associated beta-galactosidase activity in human prostate basal cells by supporting differentiation processes, but not cellular senescence.

The family of transforming growth factors betas (TGF-betas) comprises molecules involved in growth inhibition, stress-induced premature senescence, epithelial mesenchymal transition and differentiation processes. The aim of this study was to clarify the effect of long term exposure of human prostate basal cells to TGF-betas, which are found in high concentrations in prostatic fluid and areas of benign prostatic hyperplasia (BPH). Basal cell cultures established from prostate explants (n=3) were either grown into cellular senescence, or stimulated with TGF-beta1, beta2 and beta3. Similar to cellular senescence, TGF-beta stimulation resulted in an increase of SA-beta galactosidase (SA-beta-gal) activity, flattened and enlarged cell morphology, and down-regulation of the inhibitor of differentiation Id-1. TGF-beta-treated prostate epithelial cells neither showed terminal growth arrest nor induction of important senescence-relevant genes, such as p16(INK4A), IFI-6-16, IGFBP-3 or Dkk-3. Cells stained positive for cytokeratins 8/18, but did not express other lumenal markers, such as prostate-specific antigen and androgen-receptors. TGF-betas increased also the expression of the mesenchymal marker vimentin, indicating that basal epithelial cells underwent differentiation with lumenal and mesenchymal features. In contrast, in vitro-differentiated neuroendocrine-like cells from prostate organoide cultures, expressing chromogranin A and cytokeratin 18, strongly stained positive for SA-beta-gal. Thus, SA-beta-gal activity is not only a marker for senescence, but also for differentiation of human prostate epithelial cells. With regard to the in vivo situation, in addition to cellular senescence, TGF-beta could contribute to the increased number of SA-beta-gal positive epithelial cells in BPH.

Aged↗
PubMed2003

Phospholipid and cholesteryl ester transfer are increased in lipoprotein lipase deficiency.

OBJECTIVES: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism by mediating the transfer and exchange of phospholipids (PL) and neutral lipids between lipoproteins. Lipoprotein lipase (LPL) deficiency is associated with low HDL-cholesterol (HDL-C) levels in both, the homozygous and heterozygous state. In the present study we set out to investigate the role of lipid transfer proteins, which are known to strongly determine HDL-C levels, in LPL deficiency. DESIGN/SUBJECTS: Phospholipid acceptor and donor properties of lipoproteins, PLTP activity, CETP mass, activity and cholesteryl ester (CE) transfer were determined in two homozygous and six heterozygous LPL-deficient subjects and in 10 healthy, normolipidaemic controls, respectively. RESULTS: The HDL isolated from LPL-deficient subjects showed strongly increased PL-acceptance when compared with controls (homozygotes versus heterozygotes versus control: 26.46 +/- 15.26 vs. 3.41 +/- 1.61 vs. 1.89 +/- 0.33 micromol mL-1 h-1/micromol mL-1 PL; all P < 0.05). Phospholipid transfer from apolipoprotein B containing lipoproteins was increased in heterozygotes when compared with controls (46.66 +/- 23.3 vs. 28.91 +/- 18.05 micromol mL-1 h-1/micromol mL-1 PL, P = 0.05). PLTP activity, however, was similar in LPL-deficient subjects and controls. CETP mass was highest in homozygotes, whilst enzyme activity was similar in LPL-deficient subjects and controls. CE transfer was highest in homozygotes (72.5 +/- 8.8%) and lowest in controls (28.7 +/- 5.2%, P < 0.01). CONCLUSIONS: In conclusion, PL and CE transfer are increased in LPL deficiency and thus, partly explain low HDL-levels in LPL-deficient subjects. Enhanced transfer seems rather to be the result of altered lipoprotein composition and concentration than altered enzyme activity. Our findings on mechanisms leading to low HDL-C levels might show another aspect in atherogenesis in LPL deficiency.

Adult↗
PubMed2001

Hyperhomocysteinemia in bodybuilders taking anabolic steroids.

Background: Hyperhomocysteinemia has been accepted as an independent risk factor for atherosclerosis and atherothrombosis. In recent years, several reports have appeared in the literature linking the use of anabolic steroids with acute vascular events in bodybuilders. In this study, we investigated whether hyperhomocysteinemia could contribute to the high vascular risk in bodybuilders taking anabolic steroids. Methods and results: Twenty-three bodybuilders in different phases of their training cycle and six control athletes participated in our study. Anthropomorphic measures displayed a higher body mass index for bodybuilders in the competition phase than for bodybuilders in the work-out and build-up phases, and for control athletes. Homocysteine levels were 8.7+/-1.6 µmol/l (mean+/-S.D.) in control athletes, 8.5+/-2.8 µmol/l in work-out phase bodybuilders, and 8.3+/-1.5 µmol/l in competition phase bodybuilders, but 11.9+/-3.1 µmol/l in build-up phase bodybuilders (P<0.05 for build-up phase bodybuilders vs. control athletes, work-out phase bodybuilders, and competition phase bodybuilders, respectively). Vitamin B12 and folate levels did not differ significantly between the four groups. Conclusion: Our study shows that intake of anabolic steroids, as used typically by bodybuilders in the build-up phase, induces acute hyperhomocysteinemia and is likely to initiate an additional, potentially atherothrombotic mechanism in this group of athletes.

Journal Article↗
PubMed2001

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2.

AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism facilitating the transfer and exchange of cholesteryl esters, triglycerides and phospholipids between lipoproteins. In the study presented here, we investigated the influence of two hormones-the adipocyte-derived hormone leptin as well as insulin on the hepatic secretion of both, PLTP and CETP. METHODS: PLTP activity and CETP concentration-measured by exogenous substrate assay and enzyme-linked immunosorbent assay-were determined in supernatant of human hepatoma cell line HepG2 after single or combined exposure to leptin and insulin at physiological and supraphysiological concentrations, respectively. Messenger-RNA of PLTP and CETP was quantified by Northern blot analysis. RESULTS: Leptin suppressed PLTP activity and CETP-concentration by up to 33% and 23%, respectively. Insulin also suppressed PLTP activity by up to 11% and CETP-concentration by up to 16%. In combination, the two hormones had additive suppressive effects for both, PLTP activity and CETP-concentration. Northern blot analysis showed no difference in m-RNA levels after exposure to leptin or insulin. CONCLUSIONS: Leptin and insulin, both known to increase with body fat mass, suppress production of PLTP and CETP in HepG2 cells. When extrapolated to the in vivo situation, this suppressive effect may constitute a mechanism counteracting the potentially harmful action of lipid transfer proteins, particularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resistance.

Blotting, Northern↗
PubMed1999

Leptin receptor in human term placenta: in situ hybridization and immunohistochemical localization.

In the present study, we investigated the expression and localization of leptin receptors in human term placentae. On human term placenta tissue slices, digoxigenin-UTP labelled RNA-probe detected the long form of the leptin receptor ObR(L)mRNA in syncytiotrophoblasts of the villi, whereas the haematological subtype of the leptin receptor ObR/B219.1 was detected in blood cells of the intervillous space and fetal vessels. Immunohistochemistry, with two polyclonal antibodies to the N-terminus recognizing ObR(L)and ObR(S)of the leptin receptors and one to the C-terminus recognizing the long form of the leptin receptor ObR(L), localized leptin receptor protein at the apical membrane of the syncytiotrophoblasts. Our results show that the long form of the leptin receptor ObR(L)is expressed in human term placentae. We localized the long form of leptin receptor mRNA to the cytoplasm of syncytiotrophoblasts and leptin receptor proteins in human term placentae to the apical membrane of syncytiotrophoblasts. We conclude that in term placentae, leptin could mediate a growth promoting effect in the fetoplacental unit through the long form of the leptin receptor localized in the syncytiotrophoblasts. In contrast, the haematological subtype of the leptin receptor is not expressed in placental cells, but solely by blood cells in the intervillous space and fetal vessels.

Carrier Proteins↗
PubMed1998

[Leptin--an interim evaluation].

The discovery of leptin, the product of the obese (ob)-gene, has broadened the horizons of research on energy balance. This hormone, produced and secreted by adipose tissue and some placental cells, finds its way to the hypothalamus, where it binds to the leptin receptors and signals satiety through the neuroendocrine axis. The fact that adipose tissue is not merely a storage depot, but also an important endocrine tissue, has revived the interest in the "lipostatic" theory of body fat regulation and has initiated many research efforts in the field of obesity, anorexia nervosa, bulimia, reproduction and haematology.

Adipose Tissue↗