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Biomedical subjects

M T Subbiah

Publications and source records attributed to M T Subbiah.

At least 37 records · Page 2Linked to original sources
PubMed1993

Antioxidant potential of specific estrogens on lipid peroxidation.

Coronary heart disease (CHD) is the leading cause of death in postmenopause. Estrogen administration in postmenopause lowers the risk of CHD by 50%. A variety of estrogen preparations are currently used in postmenopausal hormone replacement therapy. It is unknown, however, if structural differences in the estrogen molecule influence the cardioprotective effects of estrogens. In this communication we have shown that equine estrogens (especially equilin) exhibit higher antioxidant potency (as measured by fatty acids and sterols oxidation) when compared to estrone and estradiol-17 beta.

Cell Line↗
PubMed1993

Cholesterol peroxidation potential as influenced by dietary fat type.

Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, influence of two fat vehicles, corn oil (unsaturated) or beef tallow (saturated), on cholesterol induced effects in terms of a) plasma lipoprotein peroxidation and b) aortic accumulation of cholesterol, cholesterol oxide and malonaldehyde was investigated in weanling rabbits. Although the increase in plasma cholesterol induced by cholesterol feeding was similar in both the groups Cu2+ ion induced peroxidation of lipoprotein cholesterol to oxysterols was significantly higher in corn oil group. This difference persisted even at 5 weeks after switching to chow diet. Aortic content of cholesterol and cholesterol oxides was also significantly higher in corn oil group at the end of chow diet period. Aortic accumulation of malonaldehyde (detected by immunocytochemistry) appeared to be greater in corn oil group at the end of the study. These results suggest that fatty acid composition of a given diet during exposure to high dietary cholesterol can influence cholesterol peroxidation to oxysterols and its accumulation in aorta.

Animals↗
PubMed1991

Proteins and peptides bound to long-circulating liposomes.

Liposome formulations with prolonged circulation time have recently been developed as a potential sustained-release drug delivery system. Data shown in this report indicate that such formulations can also be used to prolong the circulation time of proteins and peptides by conjugating them to the surface of liposomes. Increase of the circulation halflife ranged from 2- to 150-fold depending on the protein/lipid ratio of the liposomal formulation, liposome size, and the lipid composition of liposomes. Since the proteins/peptides localize on the liposome surface, instead of being entrapped inside the liposomes, they are directly available for binding to its receptor molecules and express the biological activity. This strategy has been successfully applied to two proteins with known fast clearance rate, i.e. asialofetuin and ricin A-chain. The biological activities of both proteins are preserved when they are formulated in liposomes. Incorporation of a peptide, i.e. a-factor of the yeast Saccharomyces cerevisiae, into the liposome membrane also significantly enhanced the circulation time of the peptide.

Animals↗
PubMed1991

Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: identification of major products and their effects.

Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.

Cells, Cultured↗
PubMed1991

Incorporation of liposomal phytosterols into human cells in culture: a potential in vitro model for investigating pathological effects of phytosterolemia.

A potential in vitro cell culture model was developed for studies concerning the pathological effect of phytosterolemia in which liposomal phytosterols were incorporated into human skin fibroblasts and hepatoblastoma (HepG2) cells. After incubation with phytosterols, fibroblasts and HepG2 cells contained a significant amount (20-27%) of phytosterols (campesterol and beta-sitosterol). Phytosterol accumulation caused a significant reduction in the cholesterol content of cells. Labeled sitosterol and cholesterol showed similar uptake with lower esterification of sitosterol when compared to cholesterol. Labeled sitosterol incorporated into LDL was esterified to a greater extent than sitosterol added as straight liposome. About 23% of the labeled sitosterol was converted into acidic products and 5.6% was present as 5 alpha-stanols in HepG2 cells.

Cells, Cultured↗
PubMed1991

Multifunctional role for fetuin (fetal protein) in lipid transport.

Recent studies from this laboratory have shown that fetuin 1) is nearly 50-fold more efficient than albumin in incorporating exogenous fatty acids into cultured cells, (JBC, 265: 5883, 1990), and 2) is associated with a lipoprotein-like particle (FASEB J. 3: 2075-2080, 1989). In the present study, this lipid-containing fraction (FLP) was isolated by ultracentrifugation, and its effect on cholesterol efflux from cultured human skin fibroblasts and Hep-G2 cells prelabeled with [14C]cholesterol was investigated. FLP fraction caused a significant efflux of [14C]cholesterol from cells, the same in magnitude as HDL. This effect of fetuin supranatant fraction increased proportionately with concentration and time. Similar results were observed with Hep-G2 cells. This ability to induce efflux of cholesterol was confirmed by a decrease in cholesterol mass of cells after 24 h incubation with FLP. The ultracentrifugal bottom (infranatant) fraction of fetuin (FI) was ineffective in this regard. However, FI was more effective in the incorporation of exogenous fatty acids into cellular triglycerides. These studies suggest that the fetuin molecule is a multifunctional protein (delivery of fatty acids to cells and cholesterol efflux from cells) which may play a role in lipid transport during fetal life.

Animals↗
PubMed1991

Newly recognized lipid carrier proteins in fetal life.

An attempt is made in this review to summarize new findings that propose the direct involvement of two fetal proteins (i.e, fetuin and alpha-fetoprotein) in fatty acid transport and delivery to cells. The presence of these proteins at a high plasma concentration in fetal life and the critical need for fatty acids during development strongly support this hypothesis. Tissue and cell specificities involved in the uptake of these fetal proteins and the mechanism of fatty acid delivery awaits further research.

Biological Transport, Active↗
PubMed1991

Plasma lipoprotein peroxidation potential: a test to evaluate individual susceptibility to peroxidation.

Peroxidation of lipids is believed to play a key role in various degenerative diseases. However, few simple tests are able to detect individual susceptibility or resistance to peroxidation. Measurement of the basal concentrations of lipid peroxides in plasma is not satisfactory because they are so low. Therefore, we developed a test to determine susceptibility of whole plasma to metal/H2O2-catalyzed peroxidation. Incubation of 300-500 microL of plasma with H2O2/cupric acetate resulted in the formation of products from fatty acids (malonaldehyde, measured by thiobarbituric acid assay) and cholesterol (predominantly cholest-3,5-dien-7-one, measured by gas-liquid chromatography). In the presence of Cu2+, formation of malonaldehyde and cholest-3,5-dien-7-one increased at least 10-fold over basal values. Lipid peroxide (malonaldehyde) and cholesterol oxide concentrations after peroxidation were significantly higher (P less than 0.01) in diabetic plasma than in normal plasma. Because susceptibility to plasma peroxidation represents a balance between pro-oxidant factors and antioxidant protection, this test may be useful in determining individual susceptibility to peroxidation as influenced by nutritional and clinical status.

Adult↗
PubMed1990

Marked acceleration of exogenous fatty acid incorporation into cellular triglycerides by fetuin.

Fetuin belongs to a group of fetal glycoproteins whose specific function is not known. In this study we investigated the effect of bovine fetuin on exogenous fatty acid incorporation into lipid classes by fetal rabbit aortic smooth muscle cells (SMC) and human fetal skin fibroblasts. When compared with albumin, the addition of fetuin to the culture medium caused a dramatic increase in labeled fatty acid incorporation (nanomoles/mg of protein) by SMC into triglycerides (albumin (control) 2.8 +/- 0.3 + fetuin 178.3 +/- 13.7). This effect was noted at a wide range of fetuin concentrations (0.2-5%) at oleate:fetuin molar ratios of 3.3-0.13, respectively. Similar effects were noted using human fetal skin fibroblasts with both labeled oleic and arachidonic acids (0.1 mM) as substrates (arachidonic acid incorporation into triglycerides, albumin (control) 76.9 +/- 16.2 + fetuin 684.6 +/- 64.1). Stimulation of fatty acid incorporation into di- and monoglycerides was also noted. Although the amount of unbound fatty acid in the presence of fetuin was greater than with albumin, experiments done under conditions that create identical unbound oleate levels (by varying fatty acid concentration) still showed increased fatty acid incorporation into triglycerides by SMC when exposed to fetuin. This marked effect of fetuin on triglyceride accumulation in cells was confirmed by lipid analysis, strong positive staining with oil red O, and transmission of electron microscopy. Furthermore, the potential physiological role of fetuin in terms of fatty acid and transport was attested by (a) the presence of significant amounts of free fatty acids associated with fetuin; and (b) by the stimulatory effect of fetuin, even when added to culture media containing other fatty acid carriers. These results show that (a) fetuin is far more efficient than albumin in incorporating fatty acids into cells; and (b) this might represent a novel function for fetuin during development.

Animals↗
PubMed1989

Fetal aortic cholesterol concentration and metabolism: relationship to plasma cholesterol and potential role of placental factors.

The relationship of fetal plasma cholesterol levels to aortic free and esterified cholesterol concentration was determined in the rabbit during gestation. Plasma cholesterol levels (mg/dl) in early fetuses were markedly high and decreased at term. While aortic free cholesterol content increased with fetal age, cholesteryl ester concentration did not change significantly and no pathological accumulation was evident. This occurred despite high fetal aortic cholesterol esterification activity noted in earlier studies. We evaluated the potential effect of rabbit placental extracts on lipid metabolism and cellular proliferation in fetal aortic explants to explore the role of placental factors in affecting lipid metabolism. Labeled [14C]oleate and [3H]thymidine were used to investigate the rates of incorporation of (a) oleate into lipids, and (b) thymidine into DNA, respectively. Placental extracts at term (but not from 22 days gestation) significantly decreased oleate incorporation (P less than 0.05) into cholesteryl esters, phospholipids and diglycerides. This effect of placental extracts was noted both in absence or presence of serum in the culture medium, and was predominantly found in fraction of Mr greater than 100,000. [3H]Thymidine incorporation (dpm/g protein) into DNA was significantly decreased (P less than 0.01) by placental extracts. These studies suggest that placental extracts contain factor(s) influencing fetal aortic lipid metabolism in culture.

Animals↗
PubMed1989

Short-term exposure to high dietary cholesterol in early life: arterial changes and response after normalization of plasma cholesterol.

Elevated serum cholesterol is an established risk factor for the development of atherosclerosis but the effect of high dietary cholesterol in early life on subsequent arterial response to atherogenic diet in adult life is unknown. Weanling rabbits were exposed for 6 wk to a diet containing 0.25% cholesterol, allowed to recover for 9 wk (at least 3 wk after normalization of plasma cholesterol), and subsequently rechallenged with cholesterol to determine atherogenic response. Enhanced activity of acyl-CoA-cholesterol-acyl-transferase in aorta induced by cholesterol feeding persisted even after normalization of serum cholesterol. When rechallenged with cholesterol for 3 mo, these animals displayed significantly (p less than 0.05) increased development of aortic atherosclerosis and accumulation of cholesterol esters when compared with control animals. Exposure to cholesterol in early life appears to cause persistent changes in cholesterol ester synthetic enzyme activity in aorta after normalization of plasma cholesterol and these residual effects might increase aortic response to subsequent cholesterol challenge in adult life.

Animals↗
PubMed1989

Association of a lipoprotein-like particle with bovine fetuin.

Fetuin is a major protein of fetal bovine serum that exhibits heterogeneity and has been found to be associated with some biological active growth factors. Preliminary studies indicated that commercial fetuin preparations contain lipids. We investigated in detail the nature of lipids associated with fetuin by using ultracentrifugation and agarose gel chromatography followed by lipid analysis. Fetuin was associated with a variety of lipids, predominantly cholesterol, cholesteryl ester with smaller amounts of phospholipids, triglycerides, and free fatty acids. Adjustment of fetuin preparation for various densities followed by ultracentrifugation resulted in a fraction with a density 1.063-1.21 g/ml (1-2% of total protein) that contained the bulk of the lipids. This fraction eluted as a single peak upon high pressure liquid chromatography and agarose gel chromatography. Delipidation of the lipoprotein-like particle followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated a major band in the range of fetuin itself. These studies suggest that a fraction of fetuin (or isoform) binds lipids forming a particle with floating characteristics similar to high density lipoproteins.

Animals↗
PubMed1988

Isolation and characterization of a novel lipoprotein particle from human placental extracts.

While it is believed that placental tissue is very active in lipid metabolism, the nature of lipid containing particles secreted (if any) by this tissue is not known. Lipoprotein profile of human placental tissue was analysed by gel filtration, gel electrophoresis and electron microscopy. Our studies demonstrated the presence of lipoproteins with unusual compositions. A novel major lipoprotein (which eluted in the same position on plasma VLDL) was characterized. While this lipoprotein floated at density greater than 1.006 gr/ml and contained apo B (same as plasma VLDL) it differed from plasma VLDL in a) size, b) contining a significant amount of apo Al, and c) carried bulk of the cholesterol (80% in free form) and phospholipids. This study suggests that placental tissue might contain unique lipoproteins perhaps serving specific metabolic needs.

Cholesterol↗
PubMed1988

Human breast-milk factors influencing lipid metabolism by fetal rabbit aorta in organ culture.

Effects of human or rabbit milk on cholesterol content, incorporation of [14C]oleate, and DNA synthesis were investigated in organ cultures of aorta from fetal and suckling rabbits. Human skim milk (50 mL/L) in organ culture decreased content (mumol/g protein) of aortic total cholesterol (control: 162.9 +/- 24.6 milk: 117.6 +/- 4.9) with significant decrease in cholesteryl esters (control: 16.5 +/- 5.1, milk: 2.3 +/- 0.5). The effect was observed in lipoprotein (total cholesterol: 120.2 +/- 8.8) and lipoprotein-free (total cholesterol: 85.4 +/- 5.1) fractions with molecular weight greater than 100,000. The human milk fraction with molecular weight greater than 100,000 was also the most active in promoting [3H]thymidine incorporation into DNA in fetal aorta. Although milk stimulated the incorporation of [14C] oleate into triglycerides (control: 38.8 +/- 2.5%, milk: 82.1 +/- 4.2%), decreased incorporation to phospholipids (control: 55.0 +/- 3.0%, milk: 11.3 +/- 1.8%) was observed. These studies suggest that milk contains factors influencing aortic lipid metabolism during development.

Animals↗
PubMed1988

Regulation of cholesterol metabolism in fetal rabbit aorta: role of amniotic fluid factors.

This study shows that amniotic fluid enhances cholesterol esterification in arterial wall, as measured by in vitro assay of acyl-CoA:cholesterol acyltransferase (ACAT) activity and by incorporation of oleic acid to cholesteryl esters in cultured fetal aortas and smooth muscle cells. This property is mostly evident in the fraction of molecular weight greater than 100,000, and it is abolished by delipidation, indicating that stimulating factor is probably lipoprotein in nature. Despite an increased cholesterol esterification by the presence of amniotic fluid in medium of cultured fetal aortas, the content of cholesterol and cholesteryl esters was much lower. The cellular structures are better preserved in explants cultured with amniotic fluid than in control animals. This study indicates that amniotic fluid contains factors that may have a pronounced effect on arterial wall during development.

Amniotic Fluid↗
PubMed1988

A novel property of an aqueous guaraná extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo.

Aqueous extracts of guaraná were studied in terms of effects on the aggregation of human and rabbit platelets. Guaraná extracts have anti-aggregatory and de-aggregatory actions on platelet aggregation induced by ADP or arachidonate but not by collagen. The active material was shown to be water soluble and heat resistant and appeared to be different from salicylates, nicotinic acid or known xanthines. Guaraná extracts inhibited platelet aggregation in rabbits following either intravenous or oral administration.

Adenosine Diphosphate↗
PubMed1987

Evidence for the presence of low density and very low density lipoproteins in human amniotic fluid.

Previous analysis of amniotic fluid (AF) noted only the presence of high density lipoprotein (HDL). In this study AF lipoprotein profile was examined using gel filtration column chromatography and Ouchterlony gel diffusion. Unlike previous studies which showed only the presence of HDL, we found significant amounts of low density lipoprotein (LDL) and very low density lipoprotein (VLDL). AF-LDL and AF-VLDL were identified by reactions with anti-h-apolipoprotein AI and AII antiserum and anti-h-apolipoprotein B-antiserum, respectively. Furthermore, bulk of the cholesterol mass was carried in VLDL (53.6 +/- 7.7%) and LDL (32.5 +/- 4.3%) with minor amounts (13.9 +/- 1.3%) in HDL fraction. It is concluded that human AF contains all three lipoproteins with most of the cholesterol being carried in very low density lipoprotein fraction.

Amniotic Fluid↗