Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
This study examines activation of poly(ADP-ribose) polymerase (
PARP
) in the ileum during hemorrhage and resuscitation and determines if inhibition of
PARP
reduces organ dysfunction and metabolic acidosis. Awake, nonheparinized rats were hemorrhaged (40 mmHg, 60 min). Resuscitation used Ringer's solution (2 1/3 x shed volume) and packed red blood cells (2/3 shed volume). Ileal
PARP
activity was elevated at the end of hemorrhage (3.6-fold) and 10 min of resuscitation (5-fold). The subsequent decline in
PARP
activity observed after 60 min of resuscitation was not due to cleavage by caspase-3.
Ileum
permeability increased 10-fold and circulating liver enzymes increased 4- to 6-fold following 60 min of resuscitation in animals pretreated with 3-aminobenzoic acid, a structural analog that does not inhibit
PARP
. Pretreatment with 3-aminobenzamide (3-AB), a
PARP
inhibitor, reduced these changes, whereas posttreatment with a bolus of 3-AB was ineffective. Metabolic acidosis, accumulation of lactate, and base deficit was reduced by pretreatment with 3-AB.
PARP
is activated in the ileum by hemorrhage and by resuscitation. Activation of
PARP
contributes to organ dysfunction in the ileum and liver and appears to be central to the development of metabolic acidosis.
...
PMID:Activation of poly(ADP-ribose) polymerase in severe hemorrhagic shock and resuscitation. 1144 30
