[摘要]：The transcription factor NF-kappa B regulates the cellular response to inflammatory and oxidant stress. Although many studies have evaluated NF-kappa B activity following exposure to oxidative stress, the role of the I kappa B family of inhibitory proteins in modulating this activity remains unclear. Specifically, the function of I kappa B beta in mediating the cellular response to oxidative stress has not been evaluated. We hypothesized that blocking oxidative stress-induced NF-kappa B signaling through I kappa B beta would prevent apoptotic cell death. Using I kappa B beta knock-in mice (AKBI), in which the I kappa B alpha gene is replaced with the I kappa B beta cDNA, we show that I kappa B beta overexpression prevented oxidative stress-induced apoptotic cell death. This was associated with retention of NF-kappa B subunits in the nucleus and maintenance of NF-kappa B activity. Furthermore, the up-regulation of pro-apoptotic genes in WT murine embryonic fibroblasts (MEFs) exposed to serum starvation was abrogated in AKBI MEFs. Inhibition of apoptosis was observed in WT MEFs overexpressing I kappa B beta with simultaneous I kappa B alpha knockdown, whereas I kappa B beta overexpression alone did not produce this effect. These findings represent a necessary but not sufficient role of I kappa B beta in preventing oxidant stress-induced cell death.
