The Change of β-Adrenergic System after Cessation of Lead Exposure

For understanding a reversible or irreversible harm of β- adrenergic system in lead induced cardiovascular disease ( hypertension), We set up animal model to estimate the change of blood pressure and sympathetic nervous system after lead exposure withdrawn in the study. We address three topics in this study: (a) the relationship between withdrawal time of lead exposure and β-adrenergic receptor, plasma catecholamine level, blood pressure, and lead level in heart , aorta, and kidney in lead- induced hypertensive rats after lead exposure stopped; (b) the relationship between blood pressure and β-adrenergic receptor in heart, aorta, and kidney; (c) the estimation of relationship between lead withdrawn and the variation of β-adrenergic system. Wistar rats were chronically fed with 2% lead acetate (experimental group) and water ( control group) for 2 months. The rats were divided into 8 groups by withdrawal time of lead exposure stopped. Plasma catecholamine level was measured by high-performance liquid chromatography. Radioligand binding assay was measured by a method that fulfilled strict criteria of β- adrenergic receptor using the ligand [125I] iodocyanopindolol. The levels of lead were determined by electrothermal atomic absorption spectrometry. The results showed that a close relation between reduced lead level and the plasma catecholamine level decreased, aorta β- adrenergic receptor increased, kidney β-adrenergic receptor diminished, heart β-adrenergic receptor increased, and blood pressure dropped after lead exposure withdrawn. The study on the regulation of β-adrenergic system in lead- induced hypertension after lead withdrawn might also provide insight about the nature of this disease state

Beta-Adrenergic Receptor Density and Adenylate Cyclase Activity in Lead- Exposed Rat Brain after Cessation of Lead Exposure

To understanding the reversible or irreversible harm to the beta- adrenergic system in the brain of lead-exposed rats, this study sets up an animal model to estimate the change in the sympathetic nervous system of brain after lead exposure was withdrawn. We address the following topics in this study: (a) the relationship between withdrawal time of lead exposure and brain beta-adrenergic receptor, blood lead level, and brain lead level in lead-exposed rats after lead exposure was stopped; and (b) the relationship between lead level and beta-adrenergic receptor and cyclic AMP (c-AMP) in brain. Wistar rats were chronically fed with 2% lead acetate and water for 2 months. Radioligand binding was assayed by a method that fulfilled strict criteria of beta- adrenergic receptor using the ligand [(125)I] iodocyanopindolol. The levels of lead were determined by electrothermal atomic absorption spectrometry. The c-AMP level was determined by radioimmunoassay. The results showed a close relationship between decreasing lead levels and increasing numbers of brain beta- adrenergic receptors and brain adenylate cyclase activity after lead exposure was withdrawn. The effect of lead exposure on the beta- adrenergic system of the brain is a partly reversible condition

TCF-4 Microsatellite Instability Mutation and Expression of Splicing Forms in Human Bladder Cancer

T cell factor (TCF)-4 and β-catenin are well recognized as key regulators in many developmental processes. TCF-4 binding with β-catenin can activate the transcriptional activity of downstream target genes (e.g. c-myc and cyclin-D1). Upregulation of TCF/β-catenin activity can promote carcinogenesis in many tissues. However, its precise role in bladder cancer is still unclear. Since typical activating mutations have not been previously reported in the bladder, we examined whether TCF-4 mutations occur in human bladder carcinoma cell lines. In the present study, interestingly, TCF-4 gene mutations were found in human bladder carcinoma cell lines as shown by reverse transcription polymerase chain reaction and a sequencing method. A TCF-4 microsatellite instability (MSI) phenotype was identified to be an (A)8 repeat arising from the deletion of an A in the (A)9 coding repeat. Moreover, immunofluorescence analysis showed that the frameshift mutant of TCF-4 was exclusively localized in the nucleus of bladder cancer cells. Collectively, our data indicate that TCF-4 MSI+ and the expression of spliced forms appear in human bladder cancer cells, and suggest a role of the TCF-4-mediated signal pathway in progression of bladder cancer