Poly(ADP-ribose) polymerase triggers the microvascular mechanisms of hepatic ischemia-reperfusion injury

Activation of poly(ADP-ribose) polymerase (PARP) mediates oxidative stress-induced cell injury. We tested the hypothesis that PARP contributes to ischemia-reperfusion (I/R) damage of the liver by triggering the mechanisms of microcirculatory failure. Leukocyte- and platelet-endothelial cell interact...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2002-09, Vol.283 (3), p.G553-G560
Main Authors: Khandoga, Andrej, Enders, Georg, Biberthaler, Peter, Krombach, Fritz
Format: Article
Language:English
Subjects:
Alanine Transaminase - metabolism
Animals
Aspartate Aminotransferases - metabolism
Blood Platelets - physiology
Cell Communication
Endothelium, Vascular - pathology
Endothelium, Vascular - physiopathology
Female
Ischemia - physiopathology
Leukocytes - physiology
Liver - enzymology
Liver Circulation
Mice
Mice, Inbred Strains
Mice, Knockout - genetics
Microcirculation - physiology
P-Selectin - metabolism
Poly(ADP-ribose) Polymerases - genetics
Poly(ADP-ribose) Polymerases - metabolism
Reperfusion Injury - physiopathology
RNA, Messenger - metabolism
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Summary:Activation of poly(ADP-ribose) polymerase (PARP) mediates oxidative stress-induced cell injury. We tested the hypothesis that PARP contributes to ischemia-reperfusion (I/R) damage of the liver by triggering the mechanisms of microcirculatory failure. Leukocyte- and platelet-endothelial cell interactions as well as sinusoidal perfusion were analyzed by intravital fluorescence microscopy after lobar hepatic I/R (90 min/30 min) in C57BL/6 x 129/Sv wild-type (PARP+/+) and PARP-deficient (PARP-/-) mice. Hepatic I/R induced leukocyte/platelet-endothelial cell interactions and tissue injury in PARP+/+ mice, as indicated by impaired sinusoidal perfusion and increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) serum activities. In PARP-/- mice, however, the postischemic increase in the numbers of rolling/adherent leukocytes and platelets was significantly lower. In addition, I/R-induced translocation of CD62P as well as mRNA expression of CD62E, CD54, and CD106 were attenuated. The degree of perfusion failure was reduced and the increase in the ALT/AST activities was lower in PARP-/- mice compared with PARP+/+ mice. We conclude that PARP contributes to hepatic microvascular injury by triggering the expression/translocation of adhesion molecules and modulating leukocyte/platelet-endothelial cell interactions.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.00085.2002