Poly(ADP-ribose) polymerase and renal hypothermic preservation injury

Martin J. Mangino, Mary Ametani, Csaba Szabo, James H. Southard

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been implicated in ischemia-reperfusion injury in many tissues under normothermic conditions. The purpose of this study was to determine whether PARP contributes to mechanisms of the hypothermic ischemia-reperfusion injury that occurs when kidneys are cold stored for transplantation. Cortical tissue slice PARP enzyme activity rose significantly with prolonged cold storage and was dependent on both reperfusion and preservation quality. However, prior exposure to warm ischemia abrogated this increase. PARP protein increased with cold storage but was not dependent on reperfusion. PARP enzyme activity rose quickly after reperfusion in buffer and was not different when whole blood was used. Addition of exogenous hydrogen peroxide (3 mM) to normal renal slices significantly increased PARP activity over 4 h in the cortex but not in the medulla, but the medullary basal PARP synthesis rate was five times higher than that in the cortex. However, the reactive oxygen species (ROS) inhibitors catalase (2,000 U/ml), Trolox (200 μM), and DMSO (15 mM) did not reduce reperfusion-induced PARP activity in cold-stored cortical slices. Finally, PARP inhibitors potentiated preservation injury in isolated canine proximal renal tubules. In conclusion, canine renal PARP enzyme activity rises with prolonged cold storage after reperfusion and may play a protective rather than an injurious role in hypothermic preservation for transplantation. ROS are sufficient but not necessary to activate PARP under these conditions.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number5 55-5
DOIs
StatePublished - May 2004
Externally publishedYes

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Poly(ADP-ribose) Polymerases
Kidney
Wounds and Injuries
Reperfusion
Enzymes
Reperfusion Injury
Canidae
Reactive Oxygen Species
Transplantation
Warm Ischemia
Proximal Kidney Tubule
Dimethyl Sulfoxide
Catalase
Hydrogen Peroxide
Buffers

Keywords

  • Adenosine 5′-triphosphate
  • Base excision system
  • Energy failure
  • NAD
  • Pharmacological inhibition
  • Reperfusion injury

ASJC Scopus subject areas

  • Physiology

Cite this

Poly(ADP-ribose) polymerase and renal hypothermic preservation injury. / Mangino, Martin J.; Ametani, Mary; Szabo, Csaba; Southard, James H.

In: American Journal of Physiology - Renal Physiology, Vol. 286, No. 5 55-5, 05.2004.

Research output: Contribution to journalArticle

Mangino, Martin J. ; Ametani, Mary ; Szabo, Csaba ; Southard, James H. / Poly(ADP-ribose) polymerase and renal hypothermic preservation injury. In: American Journal of Physiology - Renal Physiology. 2004 ; Vol. 286, No. 5 55-5.
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