The soy isoflavone, genistein, protects human cortical neuronal cells from oxidative stress.

Genistein, a soy isoflavone, has been shown to mimic the pharmacological actions of the endogenous steroid estrogen with which it has structural similarities. There is now evidence that the genistein can prevent disorders-like heart diseases, cancer and diabetes as well. However, very few studies have looked at the effect of genistein on the central nervous system. Published studies also show conflicting conclusions regarding the effects of genistein in the brain. The current study was conducted in the human cortical cell lines HCN1-A and HCN2 in order to determine the neuroprotective efficacy of genistein. It was observed that pre-treatment with 50 or 10 microM genistein was able to protect HCN1-A and HCN2 cells from the cell death induced by 100 microM or 1 mM tertiary butylhydroperoxide (t-BuOOH; a free radical generating toxin). The morphological disruption caused by t-BuOOH was also prevented by genistein in HCN2 cells. Moreover, genistein was able to prevent the down-regulation of the anti-apoptotic protein bcl-2 that was caused by t-BuOOH treatment. These results indicate that genistein may have neuroprotective effect in cortical cells, which may be mediated by its regulation of the anti-apoptotic protein bcl-2.

A comparative study of the effect of oxidative stress on the cytoskeleton in human cortical neurons.

Cytoskeleton disruption is a process by which oxidative stress disrupts cellular function. This study compares and contrasts the effect of oxidative stress on the three major cytoskeleton filaments, microfilaments (MFs), microtubule (MT), and vimentin in human cortical neuronal cell line (HCN2). HCN2 cells were treated with 100 microM tertiary butylhydroperoxide (t-BuOOH), a free radical generating neurotoxin for 1, 3, or 6 h. Cell viability studies demonstrated significant cell death although the morphology studies showed that there was a substantial loss in neurites of neurons treated with t-BuOOH for 6 h. Because the cytoskeleton plays a role in neurite outgrowth, the effect of oxidative stress on the cytoskeletal was studied. In neurons subjected to oxidative stress for 30 min or 1 h, there were no major changes in microfilament distribution though there was altered distribution of microtubule and vimentin filaments as compared to controls. However, loss and disruption of all the three cytoskeletal filaments was observed at later times (3 and 6 h), which was confirmed by Western Blot analysis. Further studies were done to measure the gene expression levels of actin, tubulin, and vimentin. Results indicated that the overall loss of the cytoskeletal proteins in neurons treated with free radical generating toxin might not be a direct result of the downregulation of the cytoskeletal genes. This study shows that free radical generation in human neurons leads to the disruption of the cytoskeleton, though there may be a difference in the susceptibility to oxidative stress among the individual components of the cytoskeletal filaments.