Genistein and daidzein induced apoA-1 transactivation in hepG2 cells expressing oestrogen receptor-alpha.

Studies have shown that soya consumption has been associated with low incidence of CVD. Because the chemical structures of soya isoflavones are similar to oestrogen, the beneficial outcome may be attributed to the oestrogenicity of these compounds. In this study, effect of the soya isoflavone genistein on the mRNA expression of apoA-1 in the human hepatoma HepG2 cell was investigated. Without oestrogen receptor (ER) alpha transfection, soya isoflavones in the physiological range had no effect on the apoA-1 transcription. Once ERalpha was ectopically expressed in these cells, soya isoflavone dramatically increased the apoA-1 mRNA abundance quantified by real-time PCR. ApoA-1-reporter assays with plasmid constructed from the 5'-flanking segment upstream to the coding region revealed that the transactivation of the apoA-1 promoter was induced by the soya isoflavone in HepG2 cells expressing ERalpha. This induction was reduced by the anti-oestrogen ICI 182780, but not the inhibitors of protein kinase (PK) C, PKA, or mitogen-activated PK. Based on the previously identified response elements on the promoter, a series of truncated promoter reporter plasmids were then constructed. An induction profile of genistein was built and insulin response core element at -411 to -404 appeared to be a potential site of interaction. This study illustrated that soya isoflavones at physiological concentrations could up regulate apoA-1 mRNA expression in ERalpha-transfected HepG2 cells.

Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex.

OBJECTIVE: To investigate the relation between biochemical alterations and disease severity in HIV-cognitive motor complex (HIV-CMC). BACKGROUND: HIV-CMC encompasses both the milder form (HIV-minor cognitive motor disorder [HIV-MCMD]) and the more severe form (HIV-dementia). There is no validated marker to monitor disease severity noninvasively. METHODS: A total of 54 patients with HIV-CMC (20 with HIV-MCMD, 34 with HIV-dementia) and 29 seronegative healthy volunteers were evaluated for cerebral metabolite abnormalities using proton (1H) MRS in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: The three subject groups showed different concentrations of myoinositol (MI; p = 0.0005) and choline-containing compounds (CHO; p = 0.004) in the frontal white matter. HIV-dementia patients had metabolite changes in all three brain regions whereas HIV-MCMD patients had abnormalities in the frontal white matter only. HIV-CMC patients had elevated MI (p < 0.0001) and CHO (p = 0.004) levels with increasing AIDS dementia complex stage, and N-acetyl compounds (NA) were decreased only in moderate to severe stages of dementia. Furthermore, CD4 count and CSF viral load, but not plasma viral load, showed significant effects on cerebral metabolite concentrations, which in turn showed significant effects on the HIV-dementia scale. CONCLUSIONS: In early stages of HIV-CMC, frontal white matter showed evidence of glial proliferation (with elevated MI and CHO levels) and cell membrane injury (with increased CHO levels), but no significant neuronal injury (with normal NA concentrations). HIV-MCMD and HIV-dementia patients have different neurochemical abnormalities. Because these biochemical alterations are related to clinical disease severity, they may be useful surrogate markers for noninvasive quantitative assessment of brain injury in patients with HIV-CMC.

Soybean protein lowers serum cholesterol levels in hamsters: effect of debittered undigested fraction.

The undigested fraction (UDF) of soybean protein exerts a marked hypocholesterolemic effect in relation to soybean protein (SOY) in rats. The present study was conducted to confirm whether UDF was effective in hamsters as in rats in combination with different fat sources, either perilla oil (PER) or safflower oil (SAF). Because the hamster, unlike the rat, disliked the bitter taste of UDF, the effect of debittering UDF also was studied. Cholesterol-enriched (0.2%) diets containing 20% protein and 10% fat were fed to hamsters for 4 wk. UDF was more hypocholesterolemic than soybean protein in hamsters regardless of the dietary fat source. The ratio of high-density lipoprotein to total cholesterol essentially remained unchanged. The debittered UDF, without influencing food intake and thereby weight gain, exerted a significant hypocholesterolemic effect comparable with UDF in relation to SOY accompanying stimulation of fecal neutral and acidic steroid excretion. The fatty acid composition of liver phospholipids was influenced by the type of the dietary protein, and both UDF seemed to interfere characteristically more than SOY with the desaturation systems between linoleic acid and arachidonic acid. Thus, the debittered UDF, similar to UDF, exerted a distinct influence on the various parameters of lipid metabolism in relation to SOY.

Effect of dietary fats on cholesterol metabolism and eicosanoid production in hamsters fed undigested fraction of soybean protein.

The undigested fraction of soybean protein (UDF) exerts a markedly greater hypocholesterolemic effect than soybean protein itself in rats. The present study was undertaken to confirm the effect in hamsters, a more appropriate animal model for human cholesterol metabolism. Hamsters were given diets containing UDF at a nitrogen level equivalent to the 20% casein diet. Dietary fats, at the 10% level, were perilla oil and safflower oil. There was apparently no increase in the serum and liver cholesterol levels in both groups of animals cholesterol-enriched diets that had been fed for 38 days. Fecal excretion of neutral and acidic steroid tended to be higher in the perilla oil group than in the safflower oil group. The perilla oil group significantly increased 20:5n-3 in liver phosphatidylcholine and phosphatidylethanolamine accompanying a decrease in 20: 4n-6. Such changes were not so evident in liver phosphatidylinositol. The production of leukotriene B4 and the concentration of prostaglandin E2 in the spleen were higher in the safflower oil group than in the perilla oil group. Thus, the hypocholesterolemic effect of the undigested fraction of soybean protein was apparently reproduced even in hamsters. Dietary fat-induced changes in lipid parameters in hamsters resembled those observed in rats.

Peroxidation, vitamin E, and sickle-cell anemia.

In summary, we propose the following scheme (Figure 5) to describe the role of peroxidation in the pathophysiology of SCA. Sickle erythrocytes are more susceptible to peroxidation than are normal erythrocytes. This increased susceptibility to peroxidation is, in part, due to decreased blood vitamin E levels and abnormal membrane phospholipid organization induced by sickling. The peroxidative damage of sickle erythrocytes may accelerate or contribute to loss of cell deformability and to chronic hemolysis. Peroxidative damage can produce abnormal cellular properties, such as potassium leak and reduced filterability, and contribute to formation of ISCs. Increased red cell rigidity can initiate episodes of capillary obstruction, leading to vasoocclusive painful crises and to tissue infarction. Liver dysfunction as well as increased production of bilirubin secondary to hemolysis could result in bile sludging and decreased secretion of bile salts into the intestinal lumen. Reduced bile salt secretion leads to partial fat and vitamin E malabsorption. Vitamin E deficiency enhances red cell susceptibility to peroxidation and promotes a vicious cycle in SCA. Although we have not studied factors that might initiate peroxidative damage, sickle hemoglobin and excess body iron should be considered as potential sources. Our studies suggest that vitamin E supplementation to sickle-cell patients could be of clinical benefit.