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Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver.

Publication ,  Journal Article
Sindram, D; Kohli, V; Madden, JF; Clavien, PA
Published in: Transplantation
July 15, 1999

BACKGROUND: Cold preservation of the liver followed by reperfusion results in sinusoidal endothelial cell (SEC) apoptosis. Calpain-like activity is dramatically increased during reperfusion and inhibition of calpains results in lower graft injury and longer survival. Recently, calpains have been implicated in inducing apoptosis. Our aim was to determine the effect of calpain inhibition on SEC apoptosis. METHODS: Livers were stored in the University of Wisconsin solution for 24 hr (survival conditions) and 40 hr (nonsurvival conditions) and ex vivo reperfused for 1 hr at 37 degrees C. Calpain-like activity was inhibited in some experiments using an i.p. injection of a selective inhibitor 2 hr before explantation. Apoptosis was quantified using the terminal deoxynucleotidyl trans. ferase-mediated dUTP nick end-labeling assay. Cross-inhibition by the inhibitor was determined for caspases 1 and 3. RESULTS: Apoptosis of exclusively the SEC was a key feature of reperfusion injury after both storage periods in University of Wisconsin solution after 1 hr normothermic reperfusion. Inhibition of calpain activity with Cbz-Val-Phe methyl ester resulted in a 50% reduction of apoptotic SEC in the 40-hr preserved liver, and an almost complete abrogation of SEC apoptosis after 24 hr preservation. Only minimal cross-inhibition of caspases was determined at high concentrations in vitro by the calpain inhibitor. CONCLUSION: Apoptosis of exclusively SEC is a key feature of reperfusion injury partially mediated through calpain-dependent processes. Calpain inhibition reduces the number of apoptotic SEC. Based on these data and our previous work, calpain inhibition may prove to be useful in clinical transplantation.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

July 15, 1999

Volume

68

Issue

1

Start / End Page

136 / 140

Location

United States

Related Subject Headings

  • Surgery
  • Reperfusion Injury
  • Rats, Wistar
  • Rats
  • Organ Preservation
  • Liver
  • Endothelium
  • Dipeptides
  • Cysteine Proteinase Inhibitors
  • Cryopreservation
 

Citation

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ICMJE
MLA
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Sindram, D., Kohli, V., Madden, J. F., & Clavien, P. A. (1999). Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver. Transplantation, 68(1), 136–140. https://doi.org/10.1097/00007890-199907150-00025
Sindram, D., V. Kohli, J. F. Madden, and P. A. Clavien. “Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver.Transplantation 68, no. 1 (July 15, 1999): 136–40. https://doi.org/10.1097/00007890-199907150-00025.
Sindram D, Kohli V, Madden JF, Clavien PA. Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver. Transplantation. 1999 Jul 15;68(1):136–40.
Sindram, D., et al. “Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver.Transplantation, vol. 68, no. 1, July 1999, pp. 136–40. Pubmed, doi:10.1097/00007890-199907150-00025.
Sindram D, Kohli V, Madden JF, Clavien PA. Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver. Transplantation. 1999 Jul 15;68(1):136–140.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

July 15, 1999

Volume

68

Issue

1

Start / End Page

136 / 140

Location

United States

Related Subject Headings

  • Surgery
  • Reperfusion Injury
  • Rats, Wistar
  • Rats
  • Organ Preservation
  • Liver
  • Endothelium
  • Dipeptides
  • Cysteine Proteinase Inhibitors
  • Cryopreservation