Oxidative stress is considered to be an important pathophysiological condition to promote cell de... more Oxidative stress is considered to be an important pathophysiological condition to promote cell death in a broad variety of disorders, such as cardiovascular and neurodegenerative diseases. Scavestrogens, structurally derived from estradiol, are potent radical scavengers and inhibitors of iron-induced cell damage in vitro. In this study the potential cytoprotective effects of the so-called scavestrogen estra-1,3,5(10),8-tetraene-3,17alpha-diol, J 811, was tested using rat cerebellar granule cells (CGCs) exposed to 25 or 50 microM hydrogen peroxide (H2O2). H2O2-induced apoptotic cell death was detected by the appearance of high molecular weight DNA fragments and nuclear condensation. The addition of J 811 before or shortly after the exposure to H2O2 prevented CGC apoptosis in a dose-dependent manner. The estrogen receptor antagonist ICI 182.780 failed to prevent the protective effect of J 811, suggesting that the latter is not dependent on estrogen receptor activation. The lack of protection against apoptosis caused by colchicine suggests that J 811 is neither interfering with the activation of caspase-3, nor acting downstream of caspase-3. Therefore, the protective effect observed against H2O2 seems to be upstream caspases activation, pointing to a scavenging action of J 811. Thus the scavestrogen J 811 is a powerful antioxidant able to interfere with radical-mediated cell death and is potentially useful in diseases where reactive oxygen species are involved.
Consider the unit measure $\mu _{F_n }$ associating the mass ${{1{\kern 1pt} } \mathord{\left/ {\... more Consider the unit measure $\mu _{F_n }$ associating the mass ${{1{\kern 1pt} } \mathord{\left/ {\vphantom {{1{\kern 1pt} } n}} \right. \kern-0em} n}$ with n points on a smooth surface in $\mathbb{R}^d ,d \geqslant 3$ , minimizing discrete energy under the influence of an external field $f$ . We call such points weighted extremal points. How well do the $\mu _{F_n }$ approximate the $f$ -weighted equilibrium distribution $\mu _f$ of the surface? We answer this question by presenting sharp estimates for the difference of the potentials of $\mu _{F_n }$ and $\mu _f$ , for the discrete energy of $\mu _{F_n }$ and for the discrepancy $\left| {\mu _{F_n } \left( B \right) - \mu _f \left( B \right)} \right|$ , where the supremum is taken over a reasonable class of test sets B. In the unweighted case f=0, extremal points reduce to d-dimensional Fekete points, and, up to a logarithmic term, the presented discrepancy estimate solves a conjecture of J. Korevaar [13].
Abstract: Investigations that revealed increased levels of iron in postmortem brains from patient... more Abstract: Investigations that revealed increased levels of iron in postmortem brains from patients with Parkinson's disease (PD) as compared to those from individuals not suffering from neurological disorders are reported. The chemical natures in which iron predominates in the brain and the relevance of neuromelanin for neuronal iron binding are discussed. Major findings have been that iron levels increase with the severity of neuropathological changes in PD, presumably due to increased transport through the blood-brain barrier in late stages of parkinsonism. Glial iron is mainly stored as ferric iron in ferritin, while neuronal iron is predominantly bound to neuromelanin. Iron overload may induce progressive degeneration of nigrostriatal neurons by facilitating the formation of reactive biological intermediates, including reactive oxygen species, and the formation of cytotoxic protein aggregates. There are indications that iron-mediated neuronal death in PD proceeds retrogradely. These results are also discussed with respect to their relevance for disease progression in relation to cytotoxic α-synuclein protofibril formation.
Oxidative stress is considered to be an important pathophysiological condition to promote cell de... more Oxidative stress is considered to be an important pathophysiological condition to promote cell death in a broad variety of disorders, such as cardiovascular and neurodegenerative diseases. Scavestrogens, structurally derived from estradiol, are potent radical scavengers and inhibitors of iron-induced cell damage in vitro. In this study the potential cytoprotective effects of the so-called scavestrogen estra-1,3,5(10),8-tetraene-3,17alpha-diol, J 811, was tested using rat cerebellar granule cells (CGCs) exposed to 25 or 50 microM hydrogen peroxide (H2O2). H2O2-induced apoptotic cell death was detected by the appearance of high molecular weight DNA fragments and nuclear condensation. The addition of J 811 before or shortly after the exposure to H2O2 prevented CGC apoptosis in a dose-dependent manner. The estrogen receptor antagonist ICI 182.780 failed to prevent the protective effect of J 811, suggesting that the latter is not dependent on estrogen receptor activation. The lack of protection against apoptosis caused by colchicine suggests that J 811 is neither interfering with the activation of caspase-3, nor acting downstream of caspase-3. Therefore, the protective effect observed against H2O2 seems to be upstream caspases activation, pointing to a scavenging action of J 811. Thus the scavestrogen J 811 is a powerful antioxidant able to interfere with radical-mediated cell death and is potentially useful in diseases where reactive oxygen species are involved.
Consider the unit measure $\mu _{F_n }$ associating the mass ${{1{\kern 1pt} } \mathord{\left/ {\... more Consider the unit measure $\mu _{F_n }$ associating the mass ${{1{\kern 1pt} } \mathord{\left/ {\vphantom {{1{\kern 1pt} } n}} \right. \kern-0em} n}$ with n points on a smooth surface in $\mathbb{R}^d ,d \geqslant 3$ , minimizing discrete energy under the influence of an external field $f$ . We call such points weighted extremal points. How well do the $\mu _{F_n }$ approximate the $f$ -weighted equilibrium distribution $\mu _f$ of the surface? We answer this question by presenting sharp estimates for the difference of the potentials of $\mu _{F_n }$ and $\mu _f$ , for the discrete energy of $\mu _{F_n }$ and for the discrepancy $\left| {\mu _{F_n } \left( B \right) - \mu _f \left( B \right)} \right|$ , where the supremum is taken over a reasonable class of test sets B. In the unweighted case f=0, extremal points reduce to d-dimensional Fekete points, and, up to a logarithmic term, the presented discrepancy estimate solves a conjecture of J. Korevaar [13].
Abstract: Investigations that revealed increased levels of iron in postmortem brains from patient... more Abstract: Investigations that revealed increased levels of iron in postmortem brains from patients with Parkinson's disease (PD) as compared to those from individuals not suffering from neurological disorders are reported. The chemical natures in which iron predominates in the brain and the relevance of neuromelanin for neuronal iron binding are discussed. Major findings have been that iron levels increase with the severity of neuropathological changes in PD, presumably due to increased transport through the blood-brain barrier in late stages of parkinsonism. Glial iron is mainly stored as ferric iron in ferritin, while neuronal iron is predominantly bound to neuromelanin. Iron overload may induce progressive degeneration of nigrostriatal neurons by facilitating the formation of reactive biological intermediates, including reactive oxygen species, and the formation of cytotoxic protein aggregates. There are indications that iron-mediated neuronal death in PD proceeds retrogradely. These results are also discussed with respect to their relevance for disease progression in relation to cytotoxic α-synuclein protofibril formation.
Uploads
Papers by Mario Gotze