Oxidant XXXX type C-deficient cells is dependent on a redox-regulated apoptotic pathway.

@entity274 @entity25087 @entity7366 @entity74 @entity2131 @entity11807
@entity11807 is a @entity74 characterized by @entity2131 . Significant evidence supports enhanced apoptosis of hematopoietic stem/progenitor cells as a critical factor in the pathogenesis of @entity2131 in @entity11807 . However, the molecular mechanism(s) responsible for the apoptotic phenotype are incompletely understood. Here, we tested whether alterations in the activation of a redox-dependent pathway may participate in the pro-apoptotic phenotype of primary @entity7366 -/- cells in response to oxidative stress. Our data indicate that @entity7366 -/- cells are highly sensitive to oxidant stimuli and undergo enhanced oxidant-mediated apoptosis compared with wild type controls. In addition, antioxidants preferentially enhanced the survival of @entity7366 -/- cells. Because oxidative stress activates the redox-dependent @entity25087 pathway, we assessed whether @entity7366 -/- cells exhibited increased oxidant-induced @entity25087 activation. Our results revealed @entity25087 hyperactivation in @entity274 -treated @entity7366 -/- cells. Furthermore, using small interfering RNAs to decrease @entity25087 expression and a dominant negative @entity25087 mutant to inhibit @entity25087 kinase activity, we determined that @entity274 -induced apoptosis was @entity25087 -dependent. Collectively, these data argue that the predisposition of @entity7366 -/- hematopoietic stem/progenitor cells to apoptosis is mediated in part through altered redox regulation and @entity25087 hyperactivation.
