Activity based proteome profiling of serum serine hydrolases:
application in pediatric abusive head trauma
Abstract
Purpose: Traumatic brain injury (TBI), including pediatric abusive head
trauma (AHT), is the leading cause of death and disability in children
and young adults worldwide. The current understanding of trauma-induced
molecular changes in the brain of human subjects with intracranial
haemorrhage (ICH) remains inadequate and requires further investigation
to improve the outcome and management of TBI in the clinic.
Calcium-mediated damage at the site of brain injury has been shown to
activate several catalytic enzymes. Experimental design: Serine
hydrolases (SHs) are major catalytic enzymes involved in the biochemical
pathways of blood coagulation, systemic inflammation and neuronal
signaling. Here we investigated activity-based protein profiling (ABPP)
by measuring the activity status of SH enzymes in the serum of infants
with severe ICH as a consequence of AHT or atraumatic infants who died
of sudden infant death syndrome (SIDS). Results: Our proof-of-principle
study revealed significantly reduced physiological activity of dozens of
metabolic SHs in the serum of infants with severe AHT compared to the
SIDS group, with some of the enzymes being related to neurodevelopment
and basic brain metabolism.