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Lipoprotein Particles (lipoprotein + particle)
Selected AbstractsCaveolin-1 secreting LNCaP cells induce tumor growth of caveolin-1 negative LNCaP cells in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008René Bartz Abstract Caveolin-1 (Cav-1) was originally identified as a structural protein of caveolae, which is a plasma membrane domain that regulates a variety of signaling pathways involved in cell growth and migration. Here, we show that expression of Cav-1 in the Cav-1-deficient human prostate cancer cell line LNCaP both stimulates cell proliferation and promotes tumor growth in nude mice. Unexpectedly, Cav-1 expressing LNCaP (LNCaPCav-1) cells injected into one side of a nude mouse promoted tumor growth of Cav-1 negative LNCaP cells injected on the contralateral side of the same animal. The LNCaP tumors were positive for Cav-1, however, this signal was not caused by migrated LNCaPCav-1 cells, but we show that this Cav-1 was secreted by the LNCaPCav-1 tumors. We demonstrate that conditioned media from LNCaPCav-1 cells contained Cav-1 that was associated with a lipoprotein particle ranging in size from 15 to 30 nm and a density similar to high density lipoprotein particle. These results suggest that LNCaPCav-1 cells secreting Cav-1 particle produce an endocrine factor that stimulates tumor growth. © 2007 Wiley-Liss, Inc. [source] Pharmaceutical and immunological evaluation of a single-shot hepatitis B vaccine formulated with PLGA microspheresJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2002Li Shi Abstract A single-shot Hepatitis B vaccine formulation using poly(d,l)-lactide-co-glycolide acid (PLGA) microspheres as a delivery system was examined using a variety of biophysical and biochemical techniques as well as immunological evaluation in C3H mice. PLGA microsphere encapsulation of the Hepatitis B surface antigen (HBsAg), a lipoprotein particle, resulted in good recoveries of protein mass, protein particle conformational integrity, and in vitro antigenicity. Some partial delipidation of the HBsAg, however, was observed. The loading and encapsulation efficiency of HBsAg into the PLGA microspheres were measured along with the morphology and size distribution of the vaccine-loaded PLGA microspheres. The in vitro release kinetics of HBsAg from the PLGA microspheres was evaluated and found to be affected by experimental conditions such as stirring rate. HBsAg showed enhanced storage stability at 37°C in the slightly acidic pH range reported to be found inside PLGA microspheres; thus, the antigen is relatively stable under conditions of temperature and pH that may mimic in vivo conditions. The immunogenicity of the microsphere formulations of HBsAg was compared with conventional aluminum adjuvant formulated HBsAg vaccine in C3H mice. Comparisons were made between aluminum formulations (one and two injections), PLGA microsphere formulations (single injection), and a mixture of aluminum and PLGA microsphere formulations (single injection). The nine-month serum antibody titers indicate that a single injection of a mixture of aluminum and PLGA-formulated HBsAg results in equal or better immune responses than two injections of aluminum-formulated HBsAg vaccine. Based on these invitro and in vivo studies, it is concluded that HBsAg can be successfully encapsulated and recovered from the PLGA microspheres and a mixture of aluminum-adjuvanted and PLGA-formulated HBsAg can auto-boost an immune response in manner comparable to multiple injections of an aluminum-formulated vaccine. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1019,1035, 2002 [source] Myocardial metabolism of triacylglycerol-rich lipoproteins in type 2 diabetesTHE JOURNAL OF PHYSIOLOGY, Issue 13 2009You-Guo Niu Cardiac utilisation of very-low-density lipoprotein (VLDL) and chylomicrons (CM) was investigated in the ZDF rat model of type 2 diabetes, in order to define the role of triacylglycerol (TAG) metabolism in the development of contractile dysfunction. Hearts from obese diabetic and lean littermate control rats were perfused with VLDL and CM from diabetic and control rats. Metabolic fate of the lipoprotein TAG and contractile function were examined. Myocardial utilisation of both VLDL- and CM-TAG was increased in the diabetic state. Diabetic hearts oxidised diabetic lipoprotein-TAG to a greater extent than control lipoproteins; glucose oxidation was decreased. There was no difference in lipoprotein-TAG assimilation into diabetic heart lipids; diabetic lipoproteins were, however, a poor substrate for control heart tissue lipid accumulation. Although the proportion of exogenous lipid incorporated into tissue TAG was increased in diabetic hearts perfused with control lipoproteins, this effect was not seen in diabetic hearts perfused with diabetic lipoproteins. Myocardial heparin-releasable lipoprotein lipase (LPL) activity was moderately increased in the diabetic state, and diabetic lipoproteins increased tissue-residual LPL activity. Cardiac hydraulic work was decreased only in diabetic hearts perfused with diabetic CM. Compositional analysis of diabetic variant lipoproteins indicated changes in size and apoprotein content. Alterations in cardiac TAG-rich lipoprotein metabolism in type 2 diabetes are due to changes in both the diabetic myocardium and the diabetic lipoprotein particle; decreased contractile function is not related to cardiac lipid accumulation from TAG-rich lipoproteins but may be associated with changes in TAG-fatty acid oxidation. [source] Charge density profiling of circulating human low-density lipoprotein particles by capillary zone electrophoresisELECTROPHORESIS, Issue 17 2004Mine-Yine Liu Abstract Capillary zone electrophoresis (CZE) has been utilized to profile the low-density (LDL) particles in human blood serum in this study. A 5 mM sodium phosphate buffer, pH 7.40, was chosen as the most suitable CE buffer and an extensive ultrafiltration (UF) procedure was applied to purify the LDL sample. Two LDL particle species, LDL with lower mobility and LDL, with higher mobility were observed. The electropherograms were highly reproducible with good precision of effective mobilities, corrected peak areas (CPAs) and CPA ratio of LDL,/LDL. LDL particles shown on the electropherogram were also characterized by several procedures. The applications of Sigma HDL cholesterol reagent and CE on-line 2-propanol precipitation indicated that the two particle species shown in the electropherogram belong to LDL. The LDL particles were found to associate with the buoyant LDL fraction and the LDL, particles associate with the dense LDL fraction. This study utilizes CZE for the profiling of LDL isoforms and provides a new analytical method for the resolution of LDL subspecies. It demonstrates a high-mobility LDL particle which circulates in healthy subjects and diminishes in atherosclerotic patients. Diminution of the high-mobility LDL subspecies may be linked to minimal formation of arterial plaque in atherosclerotic patients. [source] Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2006M. Granér Abstract Background, Remnant lipoprotein particles (RLPs) and oxidative stress are components of postprandial state. We investigated the concentrations of triglyceride-rich lipoproteins (TRLs), RLPs, low-density lipoprotein (LDL) size, and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether changes among these variables could be associated with the severity and extent of coronary artery disease (CAD). Materials and methods, Eighty men and 27 women with clinically suspected CAD underwent quantitative coronary angiography (QCA). TRLs were isolated by density gradient ultracentrifugation before and 6 h after an oral fat load. RLPs were measured by an immunoseparation method, oxLDL by ELISA, and LDL size by gradient gel electrophoresis. Results, Triglycerides, apolipoprotein (apo) B-48, and apoB-100 concentration in Swedberg flotation units (Sf) > 400 and in Sf 12,400 fractions were markedly increased at 6 h. Postprandial cholesterol content of RLPs (RLP-C) correlated with respective triglycerides in Sf > 400 (r = 0·737) and Sf 12,400 (r = 0·857), apoB-48 in Sf > 400 (r = 0·710) and Sf 12,400 (r = 0·664), apoB-100 in Sf > 400 (r = 0·812) and Sf 12,400 (r = 0·533). RLP-C correlated with oxLDL both in fasting and in fed state (r = 0·482 and r = 0·543, respectively) and inversely with LDL size (r = ,0·459 and r = ,0·442, respectively). (P < 0·001 for all). OxLDL was elevated postprandially (P < 0·001). In multivariate analysis, oxLDL was a determinant of severity and extent of CAD. Conclusion, Postprandial state is associated with oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and is associated with coronary atherosclerosis. [source] ApoB but not LDL-cholesterol is reduced by exercise training in overweight healthy men.JOURNAL OF INTERNAL MEDICINE, Issue 2 2007Exercise Study, Results from the 1-year randomized Oslo Diet Abstract. Objectives., (i) To estimate changes in apoB and apoB/apoA-I, reflecting the balance between atherogenic and anti-atherogenic lipoprotein particles, by exercise training and compare with changes in LDL-C and TC/HDL-C ratio, and (ii) To compare strengths of relationships between physical fitness and various lipoprotein variables Design, setting, and subjects., The study was a 1-year open randomized trial comprising 219 healthy middle-aged subjects aged 40,49 years who were allocated to exercise or no exercise, dietary advice or no advice in a 2 × 2 factorial design. This study includes 188 men who completed the trial, 45 to diet, 48 to exercise, 58 to diet + exercise and 37 to control. Interventions., Exercise; supervised endurance exercise three times a week. Diet; reduce weight, increase intake of fish and reduce total fat intake. Main outcome measure., One-year change in apoB and apoB/apoA-I ratio. Results., Exercisers decreased their ApoB and ApoB/ApoA-I values significantly compared to non-exercisers. LDL-C was not, but LDL-C/HDL-C was marginally but statistically significantly reduced by exercise. One-year change in ApoB and ApoB/ApoA-I correlated more strongly to 1-year changes in physical fitness than LDL-C or LDL-C/HDL-C. Adjusting for changes in LDL-C or LDL-C/HDL-C did not influence the correlation between changes in fitness and ApoB or ApoB/ApoA-I. However, adjusting for changes in ApoB or ApoB/ApoA-I wiped out the correlation between change in fitness and LDL-C or LDL-C/HDL-C. Relationships weakened when adjusting for changes in waist circumference, but Apo B or ApoB/ApoA-I still correlated significantly to changes in fitness. Conclusion., Physical exercise reduced the atherogenic burden as experienced by the reduction in apoB or apoB/apoA-I levels, but not by LDL-C in healthy middle-aged men. Possibly, regular physical activity might increase the LDL-C particle size, thereby making LDL less atherogenic. Monitoring of apolipoproteins rather than the cholesterol moiety of lipoproteins might improve the assessment of lipoprotein changes after exercise training. [source] Melatonin inhibits oxidative modification of low-density lipoprotein particles in normolipidemic post-menopausal womenJOURNAL OF PINEAL RESEARCH, Issue 3 2000Akihiko Wakatsuki In this study, we investigated the short-term effect of melatonin on the susceptibility of low-density lipoprotein (LDL) to oxidation in normolipidemic post-menopausal women. Fifteen post-menopausal women received 6.0 mg melatonin daily for 2 wk. Blood samples were obtained before and after the treatment and the plasma levels of total cholesterol, total triglyceride, high-density lipoprotein (HDL)-cholesterol, LDL-cholesterol, LDL-triglyceride, and LDL-apolipoprotein B were determined. LDL oxidation was performed by incubation with copper ions and was analyzed by monitoring the kinetics of conjugated diene formation and measuring the concentration of thiobarbituric-acid-reactive substances (TBARS). LDL-apolipoprotein B derivatization was analyzed by measuring trinitrobenzene sulfonic acid (TNBS) reactivity. Melatonin treatment significantly increased the plasma triglyceride levels (P<0.05), but did not significantly alter the plasma levels of total cholesterol, HDL-cholesterol, or LDL-lipids. The kinetics analysis of conjugated diene production revealed that melatonin treatment significantly prolonged the lag time of conjugated diene formation (from 64.71±11.89 to 70.15±10.52 min, P<0.05). The oxidation rate and the amount of conjugated diene, however, did not change significantly. The TBARS concentration was significantly reduced by melatonin treatment (from 49.31±7.57 to 38.69±23.90 nM/mg LDL, P<0.05). Furthermore, melatonin treatment significantly reduced the copper-induced decrease of TNBS reactivity (from 79.43±6.19 to 86.50±9.07% at 1 hr and from 71.03±6.74 to 76.31±4.99% at 2 hr, P<0.05). These results indicate that melatonin treatment may reduce LDL susceptibility to oxidative modification in normolipidemic post-menopausal women. [source] Cholesteryl Ester Transfer Protein (CETP) Genetic Variation and Early Onset of Non-Fatal Myocardial InfarctionANNALS OF HUMAN GENETICS, Issue 6 2008V. Meiner Summary Although Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl esters and triglycerides between lipoprotein particles and thus plays a crucial role in reverse cholesterol transport, the association of variations in the CETP gene with acute myocardial infarction (MI) remains unclear. In this study we examined whether common genetic variation in the CETP gene is related to early-onset non-fatal MI risk in a population-based case-control study from western Washington State. Genotyping for the CETP ,2708 G/A, ,971 A/G, ,629 A/C, Intron-I TaqI G/A and exon-14 A/G (I405V) SNPs was performed in 578 cases with first acute non-fatal MI and in 666 demographically similar controls, free of clinical cardiovascular disease, identified randomly from the community. In-person interviews and non-fasting blood specimens provided data on coronary heart disease risk factors. In men, there was little evidence for an association between single SNPs and MI risk, but in women the age- and race-adjusted OR was found to be significant in 4 out of the 5 CETP single variants. Haplotype analysis revealed two haplotypes associated with MI risk among men. As compared to men homozygous for the most common haplotype D (,2708 G, ,971 G, ,629 C, TaqI G and exon-14 A), the fully-adjusted multiplicative model identified haplotype G (,2708 G, ,971 A, ,629 A, TaqI G and exon-14 G) was associated with a 4.0-6.0-fold increased risk of MI for each additional copy; [95%CI 2.4,14.8] and haplotype B (,2708 G, ,971 G, ,629 A, TaqI A and exon-14 A) showed a significant decreased risk for early onset MI [OR = 0.18; 95%CI 0.04 , 0.75]. An evolutionary-based haplotype analysis indicated that the two haplotypes associated with the MI risk are most evolutionarily divergent from the other haplotypes. Variation at the CETP gene locus is associated with the risk of early-onset non-fatal MI. This association was found to be independent of HDL-C levels. These data and the sex-specific findings require confirmation in other populations. [source] | |||||||||||||