Biomedical subjects

Xueqian Wang

Publications and source records attributed to Xueqian Wang.

4 recordsLinked to original sources

PubMed2006

Upregulation of DMT1 expression in choroidal epithelia of the blood-CSF barrier following manganese exposure in vitro.

Divalent metal transporter 1 (DMT1), whose mRNA possesses a stem-loop structure in 3'-untranslated region, has been identified in most organs and responsible for transport of various divalent metal ions. Previous work from this laboratory has shown that manganese (Mn) exposure alters the function of iron regulatory protein (IRP) and increases iron (Fe) concentrations in the cerebrospinal fluid (CSF). This study was designed to test the hypothesis that Mn treatment, by acting on protein-mRNA binding between IRP and DMT1 mRNA, altered the expression of DMT1 in an immortalized choroidal epithelial Z310 cell line which was derived from rat choroid plexus epithelia, leading to a compartmental shift of Fe from the blood to the CSF. Immunocytochemistry confirmed the presence of DMT1 in Z310 cell. Following in vitro exposure to Mn at 100 microM for 24 and 48 h, the expression of DMT1 mRNA in Z310 cells was significantly increased by 45.4% (P < 0.05) and 78.1% (P < 0.01), respectively, as compared to controls. Accordingly, Western blot analysis revealed a significant increase of DMT1 protein concentrations at 48 h after Mn exposure (100 microM). Electrophoretic mobility shift assay (EMSA) showed that Mn exposure increased binding of IRP to DMT1 mRNA in cultured choroidal Z310 cells. Moreover, real-time RT-PCR revealed no changes in DMT1 heterogeneous nuclear RNA (hnRNA) levels following Mn exposure. These data suggest that Mn appears to stabilize the binding of IRP to DMT1 mRNA, thereby increasing the expression of DMT1. The facilitated transport of Fe by DMT1 at the blood-CSF barrier may partly contribute to Mn-induced neurodegenerative Parkinsonism.

Animals↗

PubMed2006

Molecular mechanism of distorted iron regulation in the blood-CSF barrier and regional blood-brain barrier following in vivo subchronic manganese exposure.

Previous studies in this laboratory indicated that manganese (Mn) exposure in vitro increases the expression of transferrin receptor (TfR) by enhancing the binding of iron regulatory proteins (IRPs) to iron responsive element-containing RNA. The current study further tested the hypothesis that in vivo exposure to Mn increased TfR expression at both blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier (BCB), which contributes to altered iron (Fe) homeostasis in the CSF. Groups of rats (10-11 each) received oral gavages at doses of 5 mg Mn/kg or 15 mg Mn/kg as MnCl(2) once daily for 30 days. Blood, CSF, and choroid plexus were collected and brain capillary fractions were separated from the regional parenchyma. Metal analyses showed that oral Mn exposure decreased concentrations of Fe in serum (-66%) but increased Fe in the CSF (+167%). Gel shift assay showed that Mn caused a dose-dependent increase of binding of IRP1 to iron responsive element-containing RNA in BCB in the choroid plexus (+70%), in regional BBB of capillaries of striatum (+39%), hippocampus (+56%), frontal cortex (+49%), and in brain parenchyma of striatum (+67%), hippocampus (+39%) and cerebellum (+28%). Real-time RT-PCR demonstrated that Mn exposure significantly increased the expression of TfR mRNA in choroid plexus and striatum with concomitant reduction in the expression of ferritin (Ft) mRNA. Collectively, these data indicate that in vivo Mn exposure results in Fe redistribution in body fluids through regulating the expression of TfR and ferritin at BCB and selected regional BBB. The disrupted Fe transport by brain barriers may underlie the distorted Fe homeostasis in the CSF.

Animals↗

PubMed2006

CNS microvascular pericytes exhibit multipotential stem cell activity.

It has been suggested that a vascular-like cell has multipotent regenerative and mesenchymal lineage relationships. The identity of this stem/progenitor cell has remained elusive. We report here that adult central nervous system (CNS) capillaries contain a distinct population of microvascular cells, the pericyte that are nestin/NG2 positive and in response to basic fibroblast growth factor (bFGF) differentiate into cells of neural lineage. In their microvascular location, pericytes express nestin and NG2 proteoglycan. In serum containing media primary (0 to 7 day old) CNS pericytes are nestin positive, NG2 positive, alpha smooth muscle actin (alphaSMA) positive, and do not bind the endothelial cell specific griffonia symplicifolia agglutinin (GSA). In serum containing media, pericytes do not undergo neurogenesis but are induced to express alphaSMA. In bFGF containing media without serum, CNS pericytes form small clusters and multicellular spheres. Differentiated spheres expressed neuronal and glial cell markers. After disruption and serial dilution, differentiated spheres were capable of self-renewal. When differentiated spheres were disrupted and cultured in the presence of serum, multiple adherent cell populations were identified by dual and triple immunocytochemistry. Cells expressing markers characteristic of pericytes, neurons, and glial cells were generated. Many of the cells exhibited dual expression of differentiation markers. With prolonged culture fully differentiated cells of neural lineage were present. Results indicate that adult CNS microvascular pericytes have neural stem cell capability.

Animals↗

PubMed2002

[Combined effect of lead and cadmium on lipid peroxidation in renal tubular epithelial cells of rats].

In order to observe the combined effects of lead and cadmium on lipid peroxidation, the cultured renal tubular epithelial cells (TEC) of rats are used to perform 3 x 3 factorial experimental design. In the experimental group (A-H), rats are given lead and cadmium respectively for 6 hours at different concentrations (A: lead acetate 0.02 mmol/L; B: lead acetate 0.1 mmol/L; C: cadmium chloride 0.001 mmol/L; D: cadmium chloride 0.004 mmol/L; E: lead acetate 0.02 mmol/L + cadmium chloride 0.001 mmol/L; F: lead acetate 0.02 mmol/L + cadmium chloride 0.004 mmol/L; G: lead acetate 0.1 mmol/L + cadmium chloride 0.001 mmol/L; H: lead acetate 0.1 mmol/L + cadmium chloride 0.004 mmol/L). After TEC are smashed by supersonic, the concentrations of glutathione (GSH) and malondiadehyde (MDA) in cells are analyzed. The same analysis is also done for the determination of the activity of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). In comparison with control group, significant decrease in activities of GSH, GSH-Px, SOD in cells treated with lead and cadmium and increases of MDA are observed. The data from ANOVA analysis show that the interaction between lead and cadmium on GSH, MDA, and SOD in TEC (P < 0.05) is demonstrated while no interaction on GSH-Px is shown.

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