Caspase-2 is essential for c-Jun transcriptional activation and Bim induction in neuron death.

Neuronal apoptotic death generally requires de novo transcription, and activation of the transcription factor c-Jun has been shown to be necessary in multiple neuronal death paradigms. Caspase-2 has been implicated in death of neuronal and non-neuronal cells, but its relationship to transcriptional activation has not been clearly elucidated. In the present study, using two different neuronal apoptotic paradigms, ß-amyloid treatment and NGF (nerve growth factor) withdrawal, we examined the hierarchical role of caspase-2 activation in the transcriptional control of neuron death. Both paradigms induce rapid activation of caspase-2 as well as activation of the transcription factor c-Jun and subsequent induction of the pro-apoptotic BH3 (Bcl-homology domain 3)-only protein Bim (Bcl-2-interacting mediator of cell death). Caspase-2 activation is dependent on the adaptor protein RAIDD {RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1ß-converting enzyme)/CED-3 (cell-death determining 3) homologue 1] protein with a death domain}, and both caspase-2 and RAIDD are required for c-Jun activation and Bim induction. The present study thus shows that rapid caspase-2 activation is essential for c-Jun activation and Bim induction in neurons subjected to apoptotic stimuli. This places caspase-2 at an apical position in the apoptotic cascade and demonstrates for the first time that caspase-2 can regulate transcription.

Commercial Sexual Exploitation and Sex Trafficking of Children and Adolescents: A Narrative Review.

Commercial sexual exploitation and sex trafficking of children and adolescents represent a severe form of child abuse and an important pediatric health concern. Youth who are commercially sexually exploited have a constellation of clinical risk factors and high rates of unmet physical and mental health needs, including conditions that directly result from their victimization. Common physical health needs among commercially sexually exploited children and adolescents include violence-related injuries, pregnancy, sexually transmitted infections, and other acute infections. Common mental health conditions include substance use disorders, post-traumatic stress disorder, depression and suicidality, and anxiety. The existing literature indicates that trauma-informed approaches to the care of commercially sexually exploited youth are recommended in all aspects of their health care delivery. Additionally, medical education that attunes providers to identify and appropriately respond to the unique needs of this highly vulnerable group of children and adolescents is needed. The available research on commercial sexual exploitation and sex trafficking of children and adolescents remains fairly limited, yet is expanding rapidly. Especially relevant to the field of pediatrics, future research to guide health professionals in how best to identify and care for commercially sexually exploited children and adolescents in the clinical setting signifies a key gap in the extant literature and an important opportunity for future study.