Eugene Rogers

Conjugated linoleic acid is a collective term used to designate a mixture of positional and geometric isomers of linoleic acid in which the double bonds are conjugated. Unlike linoleic acid, there is a paucity of information regarding the effect of dietary conjugated linoleic acid on plasma lipoproteins and aortic atherosclerosis. Therefore, fifty hamsters were divided into five groups of ten and fed 0 (Control), 0.06 (LOW), 0.11 (MEDIUM), and 1.1 (HIGH) en% conjugated linoleic acid or 1.1 en% linoleic acid. Blood samples were taken at 4, 8 and 11 weeks for plasma lipid analyses and for plasma tocopherol assay at sacrifice. Animals fed the conjugated linoleic acid-containing diets collectively had significantly reduced levels of plasma total cholesterol, non-high density lipoprotein cholesterol, (combined very low and low density lipoprotein) and triglycerides with no effect on high density lipoprotein cholesterol, as compared to CONTROLs. Linoleic acid-fed animals relative to CONTROLs also had reduced plasma total cholesterol, non-high density lipoprotein cholesterol and triglycerides, but only the latter was statistically significant. Compared to the CONTROL group, plasma tocopherol/total cholesterol ratios determined from plasma pools for the LOW, MEDIUM and HIGH conjugated linoleic acid and linoleic acid groups were increased by 48%, 48%, 86% and 29%, respectively, suggesting a tocopherol-sparing effect, at least for the conjugated linoleic acid treatment. Morphometric analysis of aortas revealed less early atherosclerosis in the conjugated linoleic acid and linoleic acid-fed hamsters compared to the CONTROL group.

Homocysteine (HC) is a neurotoxic amino acid that accumulates in several neurological disorders including Alzheimer's disease (AD). We examined the consequences of treatment of cultured murine cortical neurons with HC. Homocysteine-induced increases in cytosolic calcium, reactive oxygen species, phospho-tau immunoreactivity and externalized phosphatidyl serine (indicative of apoptosis). Homocysteine-induced calcium influx through NMDA channel activation, which stimulated glutamate excitotoxicity, as evidenced by treatment with antagonists of the NMDA channel and metabotropic glutamate receptors, respectively. The NMDA channel antagonist MK-801 reduced tau phosphorylation but not apoptosis after HC treatment, suggesting that HC-mediated apoptosis was not due to calcium influx. Apoptosis after HC treatment was reduced by co-treatment with 3-aminobenazmidine (3ab), an inhibitor of poly-ADP-ribosome polymerase (PARP), consistent with previous reports that ATP depletion by PARP-mediated repair of DNA strand breakage mediated HC-induced apoptosis. Treatment with 3ab did not reduce tau phosphorylation, however, therefore hyperphosphorylation of tau may not contribute to HC-induced apoptosis under these conditions. Inhibition of mitogen-activated protein kinase by co-treatment with the kinase inhibitor PD98059 inhibited tau phosphorylation but not apoptosis after HC treatment. HC accumulation reduces cellular levels of S-adenosyl methionine (SAM); co-treatment with SAM reduced apoptosis, suggesting that inhibition of critical methylation reactions may mediate HC-induced apoptosis. These findings indicate that HC compromises neuronal homeostasis by multiple, divergent routes.

The cause of neuronal degeneration in Alzheimer's disease (AD) has not been completely clarified, but has been variously attributed to increases in cytosolic calcium and increased generation of reactive oxygen species (ROS). The beta-amyloid fragment (Abeta) of the amyloid precursor protein induces calcium influx, ROS and apoptosis. Homocysteine (HC), a neurotoxic amino acid that accumulates in neurological disorders including AD, also induces calcium influx and oxidative stress, which has been shown to enhance neuronal excitotoxicity, leading to apoptosis. We examined the possibility that HC may augment Abeta neurotoxicity. HC potentiated the Abeta-induced increase in cytosolic calcium and apoptosis in differentiated SH-SY-5Y human neuroblastoma cells. The antioxidant vitamin E and the glutathione precursor N-acetyl-L-cysteine blocked apoptosis following cotreatment with HC and Abeta, indicating that apoptosis is associated with oxidative stress. These findings underscore that moderate accumulation of excitotoxins at concentrations that alone do not appear to initiate adverse events may enhance the effects of other factors known to cause neurodegeneration such as Abeta.

A reverse‐phase high‐performance liquid chromatography method was developed for the simultaneous separation and quantitation of tocopherols, tocotrienols and oryzanols present in rice bran oil. Tocopherols and tocotrienols were quantitated by fluorescence detection and oryzanols (ferulic acid esters of sterols and triterpene alcohols) by photodiode array detection. Chemical ionization mass spectrometry was used to identify cycloartenyl ferulate, 24‐methylene cycloartanyl ferulate, campesteryl ferulate, β‐sitosteryl ferulate and cycloartanyl ferulate as the major oryzanols separated by this procedure. The levels of these nutritionally significant components were found to vary in fully processed, edible rice bran oils from different manufacturers.