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Described is a school-focused pattern of initial and inservice training of teachers which emphasizes self evaluation and development through team membership. Details the workshop schedule and discusses activities used. (CW)

BisphenolA (BPA) is ubiquitous in the environment and is reportedto be present at high concentrations in placental tissue, where itspresence raises concerns over its potential to disrupt placental function.This report investigates how BPA interferes with the survival of humanchoriocarcinoma BeWo cells (a model of placental trophoblasts) understress-induced paradigms reminiscent of pathways activated in placentaldevelopment. These include conditions that promote oxidative stress(glutathione depletion) and apoptosis (serum withdrawal) or mimichypoxia (HIF-1α accumulation via dimethyloxalylglycine treatment).Treatment of BeWo cells with BPA during stress-induced paradigms ledto a consistent and significant increase in cell viability, with aconcomitant increase in glutathione levels and a reduction in apoptosis.Assessment of the antioxidant capacity of BPA revealed its abilityto quench reactive oxygen species and reduce the levels generatedduring glutathione and serum depletion. BPA was also able to reducethe activation of the antioxidant response element (ARE) through mediationof its activators, nuclear factor erythroid related factor familymembers (Nrf’s). Indeed, the expression and nuclear translocationof Nrf2 (an important ARE activator) were impaired by BPA, while Nrf1and Nrf3 expression levels were increased. Furthermore, BPA increasedthe levels of the anti-apoptotic proteins (Bcl-2 and Hsp70) and decreasedHIF-1α levels during stress-induced conditions. Together, theseresults indicate that BPA inhibits trophoblast cell death under conditionsof cellular stress. This could have implications on placental trophoblastsduring development. [ABSTRACT FROM AUTHOR]

The study examined how the mitochondrial enzyme monoamine oxidase-A (MAO-A), which produces hydrogen peroxide as a catalytic by-product, influences death and survival mechanisms. Targeted microRNA (miRNA) was used to stably knock down MAO-A mRNA, protein, and catalytic activity by 60-70% in SH-SY5Y human neuroblastoma cells. The effects of MAO-A knockdown (KD) on ATP, oxidative stress, electron transport chain, and survival following exposure to mitochondrial toxins were assessed. In control cells, complex I inhibition resulted in caspase-mediated cell death linked with ROS production and reduced ATP, followed by up-regulation of MAO-A mRNA, protein, and enzyme activity levels. Inhibition of complex III and IV resulted in a similar increase in MAO-A expression, while up-regulation of MAO-A was lower following complex II inhibition. MAO-A KD decreased basal reactive oxygen species levels by 50% and increased levels of ATP and reduced glutathione and Bcl-2. MAO-A KD specifically increased the activity of complex I but had no effect on complex II-IV activities. Furthermore, MAO-A KD protected against inhibitors of complex I, III, and IV. In summary, endogenous MAO-A levels influence mitochondrial function, notably complex I activity, and MAO-A may be a target for protection against neurodegenerative conditions that involve oxidative stress and mitochondrial dysfunction as underlying pathogenic factors. [ABSTRACT FROM AUTHOR]

Mitochondrial impairment, glutathione depletion and oxidative stress have been implicated in the pathogenesis of Parkinson’s disease (PD), linked recently to proteasomal dysfunction. Our study analysed how these factors influence the various activities of the proteasome in human SH-SY5Y neuroblastoma cells treated with the PD mimetics MPP+ (a complex 1 inhibitor) or dopamine. Treatment with these toxins led to dose- and time-dependent reductions in ATP and glutathione and also chymotrypsin-like and post-acidic like activities; trypsin-like activity was unaffected. Antioxidants blocked the effects of dopamine, but not MPP+, suggesting that oxidative stress was more important in the dopamine-mediated effects. With MPP+, ATP depletion was a prerequisite for loss of proteasomal activity. Thus in a dopaminergic neuron with complex 1 dysfunction both oxidative stress and ATP depletion will contribute independently to loss of proteasomal function. We show for the first time that addition of MPP+ or dopamine to purified samples of the human 20S proteasome also reduced proteasomal activities; with dopamine being most damaging. As with toxin-treated cells, chymotrypsin-like activity was most sensitive and trypsin-like activity the least sensitive. The observed differential sensitivity of the various proteasomal activities to PD mimetics is novel and its significance needs further study in human cells. [ABSTRACT FROM AUTHOR]