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Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.

Publication ,  Journal Article
Kohli, V; Madden, JF; Bentley, RC; Clavien, PA
Published in: Gastroenterology
January 1999

BACKGROUND & AIMS: Calpain proteases have been implicated in cell death by necrosis and more recently by apoptosis. Experiments were designed to determine the role of calpain proteases in ischemic rat liver injury by measurement of cytosolic calpain activity after different periods of ischemia-reperfusion and by evaluation of the effects of calpain inhibition on tissue injury and animal survival. METHODS: Calpain activity was measured in the cytosol using Suc-Leu-Leu-Val-Try-7 amino-4 methyl coumarin, a specific fluorogenic substrate, and Cbz-Leu-Leu-Tyr-CHN2, a specific inhibitor. RESULTS: Calpain activity increased significantly with the duration of ischemia-reperfusion and was inhibited more than 80% by the inhibitor. Calpain inhibition resulted in a significant decrease in transaminase release and tissue necrosis and converted nonsurvival ischemic conditions to survival conditions. When the in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling assay for apoptosis was used, 35% +/- 6% of nonparenchymal cells and 16% +/- 3% of hepatocytes stained positively after 60 minutes of ischemia and 6 hours of reperfusion. In contrast, animals pretreated with the calpain inhibitor showed minimal evidence of apoptosis. This was further substantiated by gel electrophoresis assay for DNA fragmentation and by electron-microscopic evaluation. CONCLUSIONS: These data suggest that calpain proteases play a pivotal role in warm ischemia-reperfusion injury of the rat liver through modulation of apoptosis and necrosis.

Duke Scholars

Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

January 1999

Volume

116

Issue

1

Start / End Page

168 / 178

Location

United States

Related Subject Headings

  • Reperfusion Injury
  • Rats, Wistar
  • Rats
  • Oligopeptides
  • Necrosis
  • Liver Diseases
  • Liver
  • Ischemia
  • In Situ Nick-End Labeling
  • Gastroenterology & Hepatology
 

Citation

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Kohli, V., Madden, J. F., Bentley, R. C., & Clavien, P. A. (1999). Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis. Gastroenterology, 116(1), 168–178. https://doi.org/10.1016/s0016-5085(99)70241-6
Kohli, V., J. F. Madden, R. C. Bentley, and P. A. Clavien. “Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.Gastroenterology 116, no. 1 (January 1999): 168–78. https://doi.org/10.1016/s0016-5085(99)70241-6.
Kohli V, Madden JF, Bentley RC, Clavien PA. Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis. Gastroenterology. 1999 Jan;116(1):168–78.
Kohli, V., et al. “Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.Gastroenterology, vol. 116, no. 1, Jan. 1999, pp. 168–78. Pubmed, doi:10.1016/s0016-5085(99)70241-6.
Kohli V, Madden JF, Bentley RC, Clavien PA. Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis. Gastroenterology. 1999 Jan;116(1):168–178.
Journal cover image

Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

January 1999

Volume

116

Issue

1

Start / End Page

168 / 178

Location

United States

Related Subject Headings

  • Reperfusion Injury
  • Rats, Wistar
  • Rats
  • Oligopeptides
  • Necrosis
  • Liver Diseases
  • Liver
  • Ischemia
  • In Situ Nick-End Labeling
  • Gastroenterology & Hepatology