Proteases are now firmly established as major regulators of the “execution” phase of apoptosis. Here, we examine the role of proteases and their relationship to ceramide, a proposed mediator of apoptosis, in the tumor necrosis factor-α (TNF-α)–induced pathway of cell death. Ceramide induced activation of prICE, the protease that cleaves the death substrate poly(ADP-ribose) polymerase. Bcl-2 inhibited ceramide-induced death, but not ceramide generation. In contrast, Cytokine response modifier A (CrmA), a potent inhibitor of Interleukin-1β converting enzyme and related proteases, inhibited ceramide generation and prevented TNF-α–induced death. Exogenous ceramide could overcome the CrmA block to cell death, but not the Bcl-2 block. CrmA, however, did not inhibit the activation of nuclear factor (NF)-κB by TNF-α, demonstrating that other signaling functions of TNF-α remain intact and that ceramide does not play a role in the activation of NF-κB. These studies support a distinct role for proteases in the signaling/activation phase of apoptosis acting upstream of ceramide formation.

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While a number of factors have been linked with excessive anxiety (e.g., parenting, child temperament), the impact of stressful life events remains under-studied. Moreover, much of this literature has examined bivariate associations rather than testing more complex theoretical models. The current study extends the literature on life events and child anxiety by testing a theory-driven meditational model. Specifically, one child factor (child cognitions/locus of control), two parent factors (parent psychopathology and parenting stress), and two parent-child relationship factors (parent-child dysfunctional interaction and parenting style) were examined as mediators in the relationship between stressful life events and severity of child anxiety. One hundred and thirty anxious parents and their nonanxious, high-risk children (ages ranged from 7 to 13 years) participated in this study. Results indicated that levels of parenting stress, parental anxious rearing, and dysfunctional parent-child interaction mediated the association between stressful life events and severity of anxiety symptoms. Child cognition and parent psychopathology factors failed to emerge as mediators. Findings provide support for more complex theoretical models linking life events and child anxiety and suggest potential targets of intervention.