Biomedical subjects

S X Guo-Ross

Publications and source records attributed to S X Guo-Ross.

4 recordsLinked to original sources

PubMed1999

The stabilization of ferrous iron by a toxic beta-amyloid fragment and by an aluminum salt.

Aluminum is a recognized neurotoxin in dialysis encephalopathy and may also be implicated in the etiology of neurodegenerative disease, particularly Alzheimer's disease. Alzheimer's disease is suspected to be associated with oxidative stress, possibly due to the pro-oxidant properties of beta-amyloid present in the senile plaques. The underlying mechanism by which this occurs is not well understood although interactions between amyloid and iron have been proposed. The presence of low molecular weight iron compounds can stimulate free radical production in the brain. This study provides a possible explanation whereby both aluminum and beta-amyloid can potentiate free radical formation by stabilizing iron in its more damaging ferrous (Fe2+) form which can promote the Fenton reaction. The velocity, at which Fe2+ is spontaneously oxidized to Fe3+ at 37 degrees C in 20 mM Bis-Tris buffer at pH 5.8, was significantly slowed in the presence of aluminum salts. A parallel effect of prolongation of stability of soluble ferrous ion, was found in the presence of beta-amyloid fragment (25-35). Ascorbic acid, known to potentiate the pro-oxidant properties of iron, was also capable of markedly stabilizing ferrous ions.

Alum Compounds↗

PubMed1999

Decrease of glial fibrillary acidic protein in rat frontal cortex following aluminum treatment.

Aluminum lactate was injected either intraperitoneally or stereotactically into the lateral cerebral ventricles of rats. Rats were killed at various times after treatment, and frontal cortex, hippocampus, and striatum were dissected out. Microtiter plate-based sandwich ELISA and immunohistochemistry were used to measure the glial fibrillary acidic protein (GFAP) concentration. GFAP levels were significantly decreased in frontal cortex 7 days after a single lateral ventricular injection of aluminum lactate and 14 days following systemic treatment. In contrast, neither hippocampus nor striatum exhibited any significant changes in the content of this astrocytic intermediate filament protein after aluminum treatment. Levels of a predominantly astroglial enzyme, glutamine synthetase, were also selectively reduced in the frontal cortex following intraventricular injection of aluminum. This depression exhibited a regional and temporal specificity similar to that found for GFAP. These results suggest a selective and progressive diminution of astrocytic responsivity in frontal cortex following either systemic or intraventricular aluminum dosing. The depression of GFAP levels reported here, which was found in the rat cerebral cortex 7-14 days after aluminum treatment in a species that does not form neurofilamentous aggregates, may reflect extended impairment of astrocytic function and suggests that these cells may be the primary targets of aluminum neurotoxicity.

Aluminum Compounds↗

PubMed1998

Promotion of transition metal-induced reactive oxygen species formation by beta-amyloid.

beta-amyloid protein appears to be involved in the neural degeneration associated with Alzheimer's disease. However, its mechanism of action is poorly understood. The ability of the neurotoxic peptide fragment (25-35) derived from beta-amyloid, to promote the generation of reactive oxygen species (ROS) by a postmitochondrial fraction (P2) derived from rat cerebrocortex, has been examined. The peptide fragment, when incubated together with P2, did not cause excess ROS formation. However, 10 microM FeSO4 or 10 microM CuSO4 were able to enhance ROS production in the P2 fraction and this was increased further in the concurrent presence of the 25-35 fragment. The corresponding inverse sequence non-neurotoxic peptide (35-25) had no parallel ability to augment iron-stimulated ROS production suggesting a degree of specificity for the observed effect. There was no formation of excess ROS when the 25-35 peptide and 0.5 mM Al2(SO4)3 were incubated with the P2 fraction. However in the presence of both aluminum and iron salts together with the 25-35 peptide, ROS production was augmented to a level significantly higher than that in the absence of aluminum. Polyglutamate, a peptide reported to mitigate aluminum toxicity had no effect on iron-related ROS generation but completely prevented its further potentiation by aluminum. The results indicate that beta-amyloid is able to potentiate the free-radical promoting capacity of metal ions such as iron, copper and aluminum. Such potentiation may be a relevant mechanism underlying beta-amyloid-induced degeneration of nerve cells.

Alum Compounds↗

PubMed1998

Mechanisms underlying the aluminum-induced potentiation of the pro-oxidant properties of transition metals.

Aluminum is known to enhance the ability of iron to promote the generation of reactive oxygen species (ROS) but the mechanism subserving this is unknown. In an attempt to understand the means by which this potentiation occurs, several types of experiment have been conducted. It was found that iron must be in the ferrous form for aluminum-based stimulation of ROS to take place in a cerebral cortical synaptosomal-mitochondrial fraction. The ability of other transition metals of varying valences, copper and chromium, to catalyze formation of ROS was also increased in the presence of aluminum. Catalase but not superoxide dismutase blocked such stimulation suggesting hydrogen peroxide as an intermediate. The formation of aluminosilicates in the presence of brain tissue did not enhance iron-stimulated ROS formation. Furthermore, configurational changes of proteins which have been proposed to account for this phenomenon, do not appear to be a key element since iron-aluminum potentiation could be observed using protein-free liposomal micelles bearing an external negative charge.

Aluminum↗